AVAHO

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

Should 5 mg of tamoxifen — known as “baby TAM” — or the usual 20 mg dose be standard of care for breast cancer prevention in high-risk women?

Research to date clearly shows that tamoxifen can reduce the risk for breast cancer in high-risk individuals by 30%-50%. Recent evidence also indicates that this chemoprevention approach can reduce the risk of dying from breast cancer by as much as 57%.

In 2019, the US Preventive Services Task Force issued updated recommendations that clinicians offer risk-reducing medications, such as tamoxifen, raloxifene, or aromatase inhibitors, to women at an increased risk for breast cancer and a low risk for adverse medication effects.

However, this prophylactic strategy remains underused.

A major roadblock: The drugs’ side effects, which include venous thromboembolic events and endometrial cancer as well as symptoms of menopause, such as hot flashes and sexual issues, have made uptake and adherence a challenge.

Offering women a lower dose of tamoxifen could allay fears about toxicities and improve uptake as well as reduce side effects and boost long-term adherence among those receiving baby TAM.

However, experts remain uncertain about whether patients need the standard dose to experience the full prevention benefit.
 

The Debate

Years ago, Andrea De Censi, MD, a breast cancer researcher at the Galliera Hospital in Genova, Italy, and his colleagues reasoned that, because tamoxifen is a competitive estrogen receptor inhibitor, it may indeed have a minimal effective dose below 20 mg/d.

The fruits of that line of thought were presented to the world in the TAM-01 trial, first published in 2019, which pitted tamoxifen 5 mg/d for 3 years against placebo in 500 women with high-risk lesions, including lobular and ductal carcinoma in situ.

Dr. De Censi and colleagues found that baby TAM reduced the risk for invasive breast cancer by 52% and the risk for contralateral breast cancer by 75%.

Treatment adherence was slightly higher in the baby TAM group at 65% vs 61% in the placebo group.

A recent 10-year follow-up showed ongoing benefits associated with baby TAM vs placebo — a 42% reduction in breast cancer and a 64% drop in contralateral lesions.

The baby TAM group vs placebo experienced a slight increase in hot flashes but no significant increase in other common side effects.

Regarding serious adverse events, the baby TAM arm had one case of stage 1 endometrial cancer (0.4% of patients) and 20 cases of endometrial polyps (5%) vs 13 cases of endometrial polyps in the placebo arm. But there were no significant differences in thrombosis, cataracts, bone fractures, and other serious events.

Dr. De Censi said he’s surprised the baby TAM vs tamoxifen topic is still being debated. “Baby TAM, in my opinion, is a new standard of care for endocrine prevention of breast cancer in high-risk [women],” and baby TAM over 3 years is enough, said Dr. De Censi during a debate on the topic at the 2024 European Society for Medical Oncology Breast Cancer Congress in Berlin.

Gareth Evans, MD, a cancer genetics and prevention specialist at the University of Manchester, Manchester, England, however, isn’t convinced.

During the debate, Dr. Evans explained that  his main concern was that the baby TAM trial was limited to women with high-risk lesions, not other common reasons for tamoxifen prophylaxis, such as a positive family history or BRCA mutations.

“In Manchester, we have put over a thousand women on tamoxifen who have a family history or other risk factors, not high-risk lesions,” and there simply isn’t definitive evidence for baby TAM in these women, Dr. Evans said.

The vast weight of evidence for tamoxifen prophylaxis, he added, is in trials involving tens of thousands of women, followed in some cases for 20 years, who received the 20 mg dose for 5 years.

As a result, women in Manchester are started on 20 mg and dropped down to 5 mg only for side effects. That way, Evans explained, we are not taking away the benefit among women who can tolerate 20 mg.

Meanwhile, there’s no evidence that baby TAM improves medication adherence, he noted. Trials have reported similar adherence rates to baby TAM and standard dose tamoxifen as well as no definitive evidence that the risk for cancer and thrombosis is less with baby TAM, he said.

In fact, Dr. Evans noted, “many women take tamoxifen 20 mg for 5 years with no side effects.”

Overall, “I don’t think we’ve got the evidence yet to drop” dosages, particularly in women without high-risk lesions, Dr. Evans said. A real concern, he added, is poor metabolizers for whom 5 mg won’t be enough to have a preventive effect.

Dr. De Censi noted, however, that there will likely never be a definitive answer to the question of baby TAM vs standard dosing because industry has no financial incentive to do a head-to-head trial; tamoxifen went off patent over 30 years ago.

Still, a poll of the audience favored Evans’ approach — 80% said they would start high-risk women on 20 mg for breast cancer prophylaxis and reduce for side effects as needed.

Dr. De Censi didn’t have any disclosures. Dr. Evans is a consultant/advisor for AstraZeneca, SpringWorks, Recursion, Everything Genetic, and Syantra.

A version of this article first appeared on Medscape.com.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

An elderly gentleman was truly suffering, so his doctor decided to try something new.

“He’d had a number of cumulative side effects after almost two years of IV chemotherapy for his metastatic colon cancer,” said Anuj Patel, MD, a senior physician at Dana-Farber Cancer Institute in Boston, recalling his patient. “When we switched him to combination treatment with trifluridine/tipiracil and bevacizumab, he constantly remarked on how well he now felt. He described no side effects from this new regimen.”

Nearly a year after the US Food and Drug Administration (FDA) approved trifluridine/tipiracil combined with bevacizumab for refractory mCRC, the tremendous value of its results in practice are clear.

Trifluridine/tipiracil (Lonsurf) had been used to treat advanced gastric cancer, while bevacizumab had been therapeutic for a wider range of diseases, including cervical, brain, liver, kidney, gynecological and lung cancers. Used together for treating refractory mCRC, well-known initial findings about their effectiveness have been proven true over time.

“Patients taking both drugs can experience, on average, a life extension of three months,” said Richard M. Goldberg, MD, professor emeritus of the West Virginia University Cancer Institute and director of Fight Colorectal Cancer.
 

The History of the Combined Therapy’s Approval

The FDA originally approved trifluridine/tipiracil in September 2015 for use in patients with metastatic colorectal cancer. Patients eligible to take it had to have been treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) biological therapy, and—if RAS wild-type—an anti-epidermal growth factor receptor (EGFR) therapy, according to data published by the National Center for Biotechnology Information. The FDA’s August 2023 approval of the trifluridine/tipiracil and bevacizumab combination regimen is for patients meeting the same eligibility requirements.

Another drug, regorafenib, had already been approved by the FDA in September 2012 to treat mCRC. The drug has a wide range of potential side effects, however, including complications relating to the limbs.

“One of my patients tried regorafenib as his initial third- line treatment,” Dr. Goldberg said. “I checked in on him at his farm, and he was sitting in the barn near his tractor.

He had such severe hand-foot syndrome that he could barely walk.”

Trifluridine/tipiracil alone proved to be very helpful in this case. “We switched him to it, and he tolerated it well,” Dr. Goldberg continued. “He got his fields plowed and was on it for months before he passed away. We both felt it kept him going longer.”

A new research review confirms the regimen’s success, determining that trifluridine/tipiracil plus bevacizumab was associated with improved outcomes compared to therapy solely with trifluridine/tipiracil.
 

A True Practice Changer

Now that the regimen has been on the market for more than half a year, there are longer-term data available.

Patients on average live within the same timeframe as the patients in the SUNLIGHT study, and many feel physically better on the therapy. “The combination has very quickly shifted the standard of care,” Dr. Goldberg said.

The regimen can also provide significant psychological benefits to patients.

“As patients can maintain good performance status for longer with the combination, it increases the perception of quality of life,” said Jacobo Hincapie-Echeverri, MD, a GI and geriatric oncologist at Orlando Health Cancer Institute in Orlando, Florida.

The regimen is unique too, in that it can help doctors plan additional treatment strategies.

“This current approval, for the combination of trifluridine/tipiracil and bevacizumab, is practice-changing in that it helps clarify the sequence for later treatments for patients with mCRC,” said Dr. Patel, who is also clinical director of the Center for Esophageal and Gastric Cancer and assistant professor of medicine at Harvard Medical School, Boston. “Previously, it had been difficult to decide between trifluridine/tipiracil and regorafenib in this setting.”

The fact that the regimen has been shown to give time and improved quality of life to patients in ways regorafenib does not is clarifying. “Now, with the improved outcomes seen, I do think that trifluridine/tipiracil plus bevacizumab is the better option for most mCRC patients after IV chemotherapies,” Dr. Patel added.

When it comes to his specific experience with prescribing the regimen for his patients, Dr. Patel reported that it’s easier on his patients than other therapies.

“I find that it is generally well tolerated,” he elaborated. “As an oral agent, it is also usually somewhat easier to take (than other delivery methods of medication). These factors are critical for patients who have likely already had at least 2 or 3 prior lines of chemotherapy. I have had many patients with mCRC who, after disease progression on prior IV chemotherapy regimens, have had periods of meaningful disease control – often with fewer and manageable side effects.”

Dr. Goldberg mentioned another benefit.

“The nice thing about the combination of trifluridine/tipiracil and bevacizumab is that in terms of toxicity, there’s very little difference compared to the toxicity of trifluridine/tipiracil used alone.”
 

Are There Downsides to the Regimen?

The pros are obvious, but the regimen has some cons as well. Medically, patients should have a platelet count over 75,000/mm³ and absolute neutrophil count (ANC) over 1,500/mm³ prior to the start of each cycle, and their liver and renal function should be monitored.

Patients with metastatic colorectal cancer must be also carefully monitored for hematologic adverse events (AEs) , including chemotherapy-associated neutropenia. Biweekly treatments may reduce the risk of AEs as a whole, however, according to research.

The regimen is also expensive – an approximate cost of $8,191 for a 28-day supply. According to a new study, patients managing both AE expenses along with the cost of trifluridine/tipiracil-bevacizumab face a monthly bill of about $17,179.

Some very good news, though: 100% of Medicare drug plans cover trifluridine/tipiracil, with an average copay of $57-$292. Bevacizumab is also covered by Medicare, with a copay as low as $0-$25.

Private insurers do cover the drugs, depending on a patient’s specific plan. However, if a patient’s claim is denied, financial assistance for trifluridine/tipiracil through the drug’s manufacturers may be available for some patients, reducing prescriptions to a zero cost in some cases. Bevacizumab can be made available to patients who may not have health insurance at all, too. Patients can use a financial assistance tool through the drug’s manufacturer to receive up to $25,000 in yearly copay assistance.
 

What Does the Latest Research on the Regimen Indicate?

In May 2024, two abstracts were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) that explored expanded possible use of trifluridine/tipiracil plus bevacizumab as a treatment for metastatic colorectal cancer.

The first abstract studied trifluridine/tipiracil plus bevacizumab as upfront treatment for mCRC, adding capecitabine to the regimen.

“It’s a phase 1 study looking at dose findings for the three-drug combination, where the active drug is a chemotherapy agent classified as a fluoropyrimidine ... I would characterize this as a study combining two [fluoropyrimidines] with a single targeted therapy,” Dr. Goldberg said.

“Combining two fluoropyrimidines is an unusual approach, because they tend to have overlapping side effects, and the potential is there for either innate drug resistance to the class of drugs or that the combination of two agents that work by a similar mechanism of action could hasten the development of acquired drug resistance. There is apparently a signal that combining the two chemotherapy agents enhances each other’s activity in cell culture and animal models,” he added.

Ultimately, Dr. Goldberg said he thinks more evidence is needed to prove the regimen’s effectiveness.

“This is a very early study and really provides no information about its potential given that no response data was presented,” he added. “While this is an interesting idea, it is unclear if it will pan out until we see the data on the Phase II study in progress.”

The other abstract looked at the impact of colorectal liver metastases in patients with mCRC who in phase 3 of the SUNLIGHT trial received trifluridine/tipiracil with or without bevacizumab.

“There is not much that is novel here,” Dr. Goldberg said. “The retrospective analysis shows that trifluridine/tipiracil plus bevacizumab is better than trifluridine/tipiracil alone in the subset of patients with liver metastases, as it was shown to be in the entire patient population. While this is reassuring, it’s not unexpected, especially since the vast majority of people enrolled in the SUNLIGHT trial had liver metastases.”

The Bottom Line

In the future, the potential exists for trifluridine/tipiracil combined with bevacizumab to work in first-line and second-line patients.

“Seventy percent of colorectal cancer patients reach second line treatment right now, but only 30% reach third line treatment — either they become too sick to continue, or choose not to,” Dr. Goldberg said. “The hope is that using these drugs earlier can help more patients reach and prolong treatment.”

It’s also possible that the regimen can be applied in new ways.

“Further research combining trifluridine/tipiracil and bevacizumab with other targeted therapies could yield additional advances for refractory mCRC patients,” Dr. Hincapie-Echeverri said. “The survival benefit of this therapy reinforces the importance of continuing to develop new therapies to improve outcomes in the refractory mCRC setting.”

Dr. Patel’s patient felt lucky to simply live a longer life.

Because of the regimen, “his cancer remained stable for approximately 8 months. Upon its progression, he chose not to pursue any further chemotherapy. He instead expressed his gratitude at having been able to feel more like himself for nearly a year.”

Dr. Patel received research funding in 2017 from Taiho, which manufactures trifluridine/tipiracil. He receives no current funding from Taiho and has no additional conflicts of interest. Dr. Goldberg helped represent Taiho in a patent law dispute regarding Lonsurf for which he was paid, but he is no longer paid by the company. Dr. Hincapie-Echeverri is a speaker for Astellas Pharma, which does not manufacture trifluridine/tipiracil or bevacizumab, and he has no additional conflicts of interest.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Compared with the general population, patients with urticaria had a 49% higher risk of developing cancer in the first year following diagnosis, which decreased to 6% in subsequent years, in a cohort study using Danish healthcare databases.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from Danish healthcare registries and compared the incident cancer risk between patients with urticaria and the risk in the general population.
• They identified 87,507 patients (58% women) with a primary or secondary first-time hospital outpatient clinic, emergency room, or inpatient diagnosis of urticaria between 1980 and 2022, who were followed for a median of 10.1 years.
• Incident cancers, including nonmelanoma skin cancer, were identified using the Danish Cancer Registry and classified by the extent of spread at the time of diagnosis.
• This study computed the absolute cancer risk within the first year of an urticaria diagnosis and standardized incidence ratios (SIRs), with 95% CIs standardized to Danish national cancer rates.

TAKEAWAY:

• For the first year of follow-up, the absolute risk for all cancer types was 0.7%, and it was 29.5% for subsequent years. The overall SIR for all types of cancer was 1.09 (95% CI, 1.06-1.11), which was based on 7788 observed cancer cases compared with 7161 cases expected over the entire follow-up period.
• Within the first year of follow-up, 588 patients with urticaria were diagnosed with cancer, for an SIR of 1.49 (95% CI, 1.38-1.62) for all cancer types.
• After the first year, the SIR for all cancer sites decreased and stabilized at 1.06 (95% CI, 1.04-1.09), with 7200 observed cancer cases.
• The risk was highest for hematological cancers in the first year, particularly Hodgkin lymphoma (SIR, 5.35; 95% CI, 2.56-9.85).

IN PRACTICE:

“Our study suggests that urticaria may be a marker of occult cancer and that it is associated with a slightly increased long-term cancer risk,” the authors wrote.

SOURCE:

The study was led by Sissel B.T. Sørensen, departments of dermatology and rheumatology, Aarhus University Hospital, Aarhus, Denmark. It was published online on June 27, 2024, in the British Journal of Dermatology.

LIMITATIONS:

The study is limited by its observational design and reliance on registry data, which may be subject to misclassification or incomplete information. In addition, the study could not assess individual patient factors such as lifestyle or genetic predispositions that may influence cancer risk, and the results may not be generalizable to other populations. Finally, the exact biologic mechanisms linking urticaria and cancer remain unclear, warranting further investigation.

DISCLOSURES:

The study did not receive any funding. The authors reported that they had no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in breast cancer patients, in a new study.

“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).

Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.

“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.

Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
 

Study Methods and Results

Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.

Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.

The study’s primary endpoint was the residual cancer burden at the time of surgery.

Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.

While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.

In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).

The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”

The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).

Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
 

Ideas for Further Study of Tecemotide

“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.

Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”

Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.

The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in breast cancer patients, in a new study.

“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).

Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.

“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.

Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
 

Study Methods and Results

Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.

Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.

The study’s primary endpoint was the residual cancer burden at the time of surgery.

Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.

While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.

In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).

The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”

The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).

Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
 

Ideas for Further Study of Tecemotide

“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.

Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”

Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.

The MUC-1 vaccine tecemotide plus standard neoadjuvant systemic therapy was shown to notably improve distant relapse-free survival and overall survival rates in breast cancer patients, in a new study.

“This is the first successful study of a breast cancer vaccine to date,” Christian F. Singer, MD, said during an interview. Dr. Singer, the lead author of the new study, presented the results during a poster session at the 2024 annual meeting of the American Society of Clinical Oncology (ASCO).

Previously known as both liposomal BLP25 and Stimuvax, tecemotide is an antigen-specific immunotherapy that targets the cancer therapy–resistant MUC-1 glycoprotein, which is overexpressed in over 90% of breast cancers. Tecemotide also has been shown to moderately improve overall survival rates in non–small cell lung cancer.

“We are not at all surprised by the results of this study in breast cancer,” Gregory T. Wurz, PhD, senior researcher at RCU Labs in Lincoln, California, said in an interview.

Dr. Wurz is coauthor of several studies on peptide vaccines, including a mouse model study of human MUC-1–expressing mammary tumors showing that tecemotide combined with letrozole had additive antitumor activity. Another paper he coauthored showed that ospemifene enhanced the immune response to tecemotide in both tumor-bearing and non–tumor-bearing mice. These findings, combined with other research, led to the creation of a patented method of combining therapies to enhance the efficacy of immunotherapy in the treatment of cancer and infectious diseases. Dr. Wurz was not involved in the new research that Dr. Singer presented at ASCO.
 

Study Methods and Results

Dr. Singer, head of obstetrics and gynecology at the Medical University of Vienna, Vienna, Austria, and coauthors randomized 400 patients with HER2-negative early breast cancer in a prospective, multicenter, two-arm, phase 2 ABCSG 34 trial to receive preoperative standard of care (SOC) neoadjuvant treatment with or without tecemotide.

Postmenopausal women with luminal A tumors were given 6 months of letrozole as SOC. Postmenopausal patients with triple-negative breast cancer, luminal B tumors, in whom chemotherapy was SOC, as well as all premenopausal study participants, were given four cycles of both epirubicin cyclophosphamide and docetaxel every 3 weeks.

The study’s primary endpoint was the residual cancer burden at the time of surgery.

Long-term outcomes were measured as part of a translational project, while distant relapse-free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Long-term outcome data were available for 291 women, of whom 236 had received chemotherapy as SOC.

While tecemotide plus neoadjuvant SOC was not associated with a significant increase in residual cancer burden (RCB) at the time of surgery (36.4% vs 31.5%; P = .42; 40.5% vs 34.8%; P = .37 for the chemotherapy-only cohort), follow-up at 7 years showed 80.8% of patients who had received SOC plus tecemotide were still alive and free from metastasis.

In patients who had received SOC alone, the OS rate at 7 years with no metastasis was 64.7% (hazard ratio [HR] for DRFS, 0.53; 95% CI, 0.34-0.83; P = .005). The OS rate for the study group was 83.0% vs 68.2% in the non-tecemotide cohort (HR for OS, 0.53; 95% CI, 0.33-0.85; P = .008).

The lack of RCB signal at the endpoints, “tells us that pathologic complete response and residual cancer burden simply are not adequate endpoints for cancer vaccination studies and we need to find other predictive/prognostic markers, said Dr. Singer. “We are currently looking into this in exploratory studies.”

The chemotherapy plus tecemotide cohort had a notable outcome with a DRFS of 81.9% vs 65.0% in the SOC group (HR, 0.50; 95% CI, 0.31-0.83; P = .007), and an OS rate of 83.6% vs 67.8% (HR, 0.51; 95% CI, 0.30-0.88; P = .016).

Dr. Singer characterized the HRs as intriguing, saying that they “pave the way for new trials.”
 

Ideas for Further Study of Tecemotide

“What we would like to see next for tecemotide are clinical studies that explore whether immunomodulatory agents can further enhance the response to tecemotide in lung, breast, and potentially other MUC-1–expressing cancers,” Dr. Wurz said.

Future phase 3 studies of MUC-1 cancer vaccines, possibly those using mRNA technology, are yet to come, according to Dr. Singer. “We also need to find out why the vaccine works sometimes and sometimes not.”

Dr. Singer disclosed financial ties to AstraZeneca/MedImmune, Daiichi Sankyo Europe, Novartis, Gilead Sciences, Sanofi/Aventis, Amgen, Myriad Genetics, and Roche. Dr. Wurz had no disclosures, but his research partner and founder of RCU Labs, Michael De Gregorio, is the sole inventor of the patent referenced in the story. That patent has been assigned to the Regents of the University of California.

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

A version of this article first appeared on Medscape.com.

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

A version of this article first appeared on Medscape.com.

A central aim of prostate cancer treatment is to prolong survival, but trials often overlook another key goal: Improving — or at least maintaining — quality of life (QoL).

The recent American Society of Clinical Oncology (ASCO) 2024 annual meeting dedicated a session to QoL outcomes in men with prostate cancer.

The trials explored the effects of treatment suspension or intensification on health-related QoL as well as interventions to manage side effects in different patient populations.

The first presentation focused on a post hoc analysis of the phase 3 EMBARK trial, which looked at the effect of suspending treatment on health-related QoL in men with nonmetastatic disease at a high risk for biochemical recurrence.

Earlier findings from the trial, presented at ESMO in 2023, showed enzalutamide alone or in combination with androgen deprivation therapy (ADT) was associated with a significant improvement in metastasis-free survival vs placebo plus leuprolide.

The initial trial randomized 1068 patients at a high risk for biochemical recurrence to these three treatment groups and suspended therapy at week 37 if prostate-specific antigen (PSA) levels fell below 0.2 ng/mL. Patients, however, were not randomized into the treatment suspension groups. Treatment resumed if PSA levels rose to ≥ 2.0 ng/mL in patients who had undergone radical prostatectomy or ≥ 5.0 ng/mL in those who had not had surgery.

The post hoc analysis, which assessed patient-reported QoL outcomes following treatment suspension at baseline and every 12 weeks until progression, found no meaningful changes in the worst pain in the past 24 hours, as measured by the Brief Pain Inventory–Short Form.

Patients also reported no meaningful changes in total and physical well-being scores on the Functional Assessment of Cancer Therapy–Prostate (FACT-P) and on the European Quality of Life Five-Dimensions (EuroQol-5D) visual analog scale score, as well as no meaningful changes in sexual activity and urinary and bowel symptoms, based on scores from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate 25 (QLQ-PR25).

Hormone treatment-related symptoms on the QLQ-PR25, however, “quickly improved but eventually began to worsen after week 97,” explained lead author Stephen J. Freedland, MD, from Cedars-Sinai Medical Center, Los Angeles, California, who presented the new findings at ASCO.

Dr. Freedland concluded that the EMBARK results show that enzalutamide, with or without ADT, improves metastasis-free survival vs leuprolide alone, without affecting global health-related QoL during treatment or after treatment suspension.

However, Channing J. Paller, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, Maryland, who was not involved in the research, pointed out that “patient selection is key” when choosing therapies, given that ADT has distinct adverse effects. Comorbidities and adverse effects “must be taken into consideration to help the doctor and patient make more personalized treatment choices.”
 

Treatment Intensification and QoL

Another presentation explored health-related QoL outcomes from the phase 3 PRESTO trial.

The study examined ADT intensification in 504 patients who had high-risk biochemically relapsed nonmetastatic hormone-sensitive prostate cancer and a PSA doubling time of 9 months or less. Patients were randomized to ADT monotherapy with degarelix or leuprolide, ADT plus apalutamide, or ADT plus apalutamide, abiraterone acetate, and prednisone.

In previous data from PRESTO, the combination therapy groups both had significantly longer median PSA progression-free survival than the ADT monotherapy arm.

The latest data looked at the health-related QoL outcomes in the PRESTO population, measured using the Expanded Prostate Cancer Index Composite, the PROMIS Fatigue tool, the Hot Flash Related Daily Interference Scale, and the EuroQol-5D.

Ronald C. Chen, MD, MPH, of the University of Kansas Medical Center, Kansas City, who presented the new findings at ASCO, reported that ADT plus apalutamide improved PSA progression-free survival over ADT alone and did not meaningfully increase common treatment-related symptoms, such as hormonal symptoms, sexual dysfunction, hot flash interference, and fatigue.

However, treatment intensification with triple androgen regimen did not lead to further improvements in PSA progression-free survival but did increase the rate of serious adverse events, the time to testosterone recover, and increased hot flash interference.

PRESTO as well as EMBARK “provide a strong rationale for intensification of androgen blockade in men with high-risk biochemical recurrence after completing primary local therapy” and could even “reduce the need for subsequent treatment,” concluded Dr. Chen.
 

CBT for Managing ADT Side Effects

Up to 80% of men receiving ADT to treat prostate cancer experience night sweats and hot flashes, which are associated with sleep disturbance, anxiety, low mood, and cognitive impairments.

A third trial presented during the session looked at the impact of cognitive-behavioral therapy (CBT) on these side effects of ADT treatment.

Initial findings from the MANCAN study found that CBT delivered by a psychologist reduced the impact of hot flashes and night sweats at 6 weeks.

The MANCAN2 study assessed QoL at 6 months among 162 patients with localized or advanced prostate cancer who underwent at least 6 months of continuous ADT and who experienced more severe hot flashes and night sweats, defined as a score of ≥ 2 on the hot flashes and night sweats problem rating scale.

Study participants were randomized to CBT plus treatment as usual, or treatment as usual alone, with the intervention consisting of two CBT group sessions 4 weeks apart. Between CBT sessions, patients could refer to a booklet and CD, alongside exercises and CBT strategies.

MANCAN2 confirmed that CBT was associated with a significantly greater reduction in hot flash and night sweat scores over standard care alone at 6 weeks. Patients receiving CBT also reported better QoL, sleep, and functional status but those differences did not reach statistical significance.

By 6 months, those in the CBT group still reported better outcomes in each category, but no differences were statistically significant at this time point. Overall, however, 14% of treatment as usual alone patients discontinued ADT at 6 months vs none in the CBT arm.

“Further research is therefore needed to determine whether or not you can make this effect more durable” and to look at “the potential for CBT to support treatment compliance,” said study presenter Simon J. Crabb, PhD, MBBS, from the University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, England.
 

QoL With Radioligand Crossover

Finally, the phase 3 PSMAfore study compared ¹⁷⁷Lu-PSMA-617 with abiraterone or enzalutamide in 468 taxane-naive patients with metastatic castration-resistant prostate cancer who had progressed on a previous androgen receptor pathway inhibitor.

In earlier analyses, Karim Fizazi, MD, PhD, Institut Gustave Roussy, Université Paris-Saclay, Paris, France, reported that ¹⁷⁷Lu-PSMA-617 improved radiographic progression-free survival by 59% over androgen receptor pathway inhibitor therapy but did not lead to significant differences in overall survival.

In a new interim analysis, Dr. Fizazi and colleagues explored outcomes in patients eligible to cross over to ¹⁷⁷Lu-PSMA-617 following androgen receptor pathway inhibitor therapy. Assessments of health-related QoL revealed that ¹⁷⁷Lu-PSMA-617 led to about a 40% improvement in scores on two QoL tools — 41% with FACT-P and 39% with EuroQol-5D.

On subscales of FACT-P, Dr. Fizazi reported that ¹⁷⁷Lu-PSMA-617 was also associated with a significantly longer time to worsening in physical, functional, and emotional well-being over standard therapy. A pain inventory score indicated that ¹⁷⁷Lu-PSMA-617 led to a 31% improvement in the time to worsening pain intensity, as well as a 33% increase in the time to worsening pain interference.

With the treatment having a “favorable safety profile,” Dr. Fizazi said the results suggest ¹⁷⁷Lu-PSMA-617 is a “treatment option” for patients with metastatic castration-resistant prostate cancer who have undergone androgen receptor pathway inhibitor treatment.

MANCAN2 was funded by the UK National Institute for Health and Care Research. EMBARK was funded by Astellas Pharma and Pfizer, the codevelopers of enzalutamide. PRESTO was funded by Alliance Foundation Trials and Johnson & Johnson. PSMAfore was funded by Novartis. Dr. Freedland declared relationships with Pfizer and Astellas Pharma, among others. Paller declared relationships with AstraZeneca, Dendreon, Exelixis, Janssen Oncology, Omnitura, Lilly, and Bayer. Dr. Chen declared relationships with Astellas Pharma, Pfizer, and others. Dr. Crabb declared relationships with AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Amgen, Amphista Therapeutics, Bayer, Janssen, MSD, Pfizer, Astex Pharmaceuticals, Clovis Oncology, and Roche. Dr. Fizazi reported relationships with Novartis, AstraZeneca, and a dozen other companies.

A version of this article first appeared on Medscape.com.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Not too long ago, prostate-cancer genetics didn’t mean much to patient care. But in recent years, the landscape of therapy has transformed as researchers have discovered links between multiple genes and aggressive tumors. 

Now, as a hematologist-oncologist explained to attendees at an Association of VA Hematology/Oncology regional meeting in Detroit, genetic tests can guide treatment for some—but not all—men with prostate cancer.

For patients with mutations, appropriate supplemental medications “can improve overall outcomes and have a long-standing impact on patients” said Scott J. Dawsey, MD, of the John D. Dingell Veterans Affairs Medical Center in Detroit in an interview following the AVAHO meeting, which focused on the management of prostate cancer.

As Dawsey explained, about 10% of patients with prostate cancer appear to have genetic mutations, although the exact percentage is unclear. The mutations are especially common in metastatic forms of prostate cancer. They’re estimated to be present in 11.8%-16.2% of those cases.

While these proportions are relatively small, the number of overall prostate-cancer cases with mutations is large due to the high burden of the disease, Dawsey said. Prostate cancer is by far the most common cancer in men, and estimated 299,010 cases will be diagnosed in the United States this year.

According to Dawsey, genetic mutations seem to boost the risk of more aggressive disease—and the risk of other malignancies—by disrupting DNA repair. This process can lead to even more mutations that may “make the cancer behave and grow more aggressively.”

But not all prostate cancer patients need to undergo genetic testing. Dawsey urged colleagues to figure out which patients should be tested by consulting National Comprehensive Cancer Network (NCCN) guidelines and the newly updated US Department of Veterans Affairs (VA) prostate cancer clinical pathway.

The two sets of recommendations agree on germline testing in patients with cases that are metastatic, very high risk, and high risk. Lower-risk cases should only be tested if patients meet family history criteria. The sets of guidelines also recommend somatic testing in patients with metastatic cancer.

In addition to providing guidance about treatment, genetic test results can have implications regarding other potential malignancies that may affect patients, Dawsey said. The results may also have implications for cancer risk in family members.

Several drugs are now available for patients with genetic mutations, including checkpoint inhibitors and PARP inhibitors. The drugs, which have unique mechanisms of action, are given in addition to standard prostate cancer treatments, he said.

“If a patient doesn’t have one of these genetic changes,” he said, “these drugs aren’t an option.”

A long list of drugs or combinations of drugs are in clinical trials, including the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors olaparib, abiraterone, and niraparib and the checkpoint inhibitors nivolumab and cemiplimab.

The drugs generally improve response rates and progression-free survival, Dawsey said, and patients are generally able to tolerate them. In regard to which drugs to choose, he suggested consulting the and NCCN guidelines and the VA oncology clinical pathway for prostate cancer.

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

Findings from the phase 3 ESOPEC trial demonstrate an overall survival advantage with a perioperative chemotherapy regimen known as FLOT, compared with a neoadjuvant chemoradiation approach, called CROSS, in patients with resectable, locally advanced esophageal adenocarcinoma.

The study results, presented as a late-breaking abstract at the annual meeting of the American Society of Clinical Oncology (ASCO), help settle a long-standing debate about whether chemotherapy with FLOT — 5-florouracil, leucovorin, oxaliplatin, and docetaxel — before and after surgery, or neoadjuvant radiation plus CROSS — carboplatin and paclitaxel — followed by surgery is the best approach.

There has been “considerable disagreement as to whether giving all adjuvant therapy upfront versus ‘sandwich’ adjuvant therapy before and after surgery is the better standard of care for locally advanced resectable esophageal cancer,” Jennifer Tseng, MD, of Boston Medical Center, Boston, said in an ASCO press release. This randomized clinical trial shows the sandwich approach “provides better outcomes.”

The practice-changing ESOPEC findings will have an important effect on the management of patients with resectable esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma, but local and distant failures remain a challenge in this population, explained invited discussant Karyn A. Goodman, MD.

Advances since the initiation of ESOPEC — such as immunotherapy options and personalized strategies — suggest the esophageal adenocarcinoma story is still evolving, said Dr. Goodman, professor and vice chair of research and quality in the Department of Radiation Oncology at Icahn School of Medicine at Mount Sinai, New York. 
 

The ESOPEC trial

Both the FLOT and CROSS regimens are established standards of care in resectable esophageal adenocarcinoma, and the choice of treatment has largely varied based on geographical location.

The current randomized, prospective, open-label ESOPEC trial, however, demonstrated that FLOT can prolong overall survival, first author Jens Hoeppner, MD, from the University of Bielefeld in Detmold, Germany, reported.

Overall, 438 patients with locally advanced, resectable esophageal adenocarcinoma recruited between February 2016 and April 2020 from 25 sites in Germany and randomized to either FLOT (n = 221) or CROSS (n = 217). The median age was 63 years, and most (89.3%) were men. Patients were followed until November 2023, and median follow-up was 55 months.

Patients in the FLOT arm received four cycles — one every 2 weeks for 8 weeks — followed by surgery 4-6 weeks later. FLOT cycles were reinitiated 4-6 weeks after surgery and given every 2 weeks for 8 weeks.

Those in the CROSS arm received one cycle per week of radiation therapy for 5 weeks plus carboplatin and paclitaxel followed by surgery 4-6 weeks after the last cycle.

Overall, 86% received both neoadjuvant therapy and surgery in the FLOT arm versus 82.9% in the CROSS group. Among these patients, 16.8% in the FLOT group achieved a pathological complete remission versus 10.0% in the CROSS arm.

In the intention-to-treat population, median overall survival was almost twice as long in the FLOT group — 66 months versus 37 months. At 3 years, those who received FLOT had a 30% lower risk of dying (hazard ratio [HR], 0.70), with 57.4% of patients alive at that point, compared with 50.7% patients in the CROSS arm.

The 5-year overall survival was 50.6% in the FLOT group versus 38.7% in the CROSS group.

Patients receiving FLOT also demonstrated improved progression-free survival (PFS), with a median PFS of 38 months versus 16 months. The 3-year PFS was 51.6% with FLOT versus 35.0% with CROSS (HR, 0.66). The exploratory subgroup analyses for sex, age, ECOG status, and clinical T and N stages also favored FLOT.

The 30-day postoperative mortality was 1.0% in the FLOT group and 1.7% in the CROSS group, and the 90-day postoperative mortality rate was 3.2% and 5.6%, respectively.

Based on these findings, perioperative chemotherapy with FLOT should be preferred over neoadjuvant chemoradiation with CROSS, Dr. Hoeppner concluded.

Dr. Goodman agreed, noting that, in the wake of ESOPEC, FLOT will likely be adopted as a more standard approach in the United States for patients who are fit. And, for patients who are not candidates for FLOT, CROSS is a reasonable option, she said.

But, she asked, does it really have to be an either/or situation?

Multiple studies, including Dr. Goodman’s 2021 Alliance/CALGB 80803 study, have demonstrated promising outcomes with combined modalities and adapting therapy based on treatment response. Several trials, for instance, are evaluating combining FLOT and CROSS, with some showing the approach is feasible and comes with manageable toxicity.

It’s also important to look outside of FLOT and CROSS. During ESOPEC, new approaches entered the treatment landscape, including the use of adjuvant immunotherapy following neoadjuvant chemoradiation and surgery for noncomplete response.

Take the CheckMate 577 study, which found that adjuvant nivolumab immunotherapy after preoperative CROSS and surgery significantly reduced metastatic recurrence and doubled disease-free survival in patients who did not achieve a complete response. This approach is now a standard of care for those patients.

FLOT plus neoadjuvant nivolumab may also be a viable option, Dr. Goodman noted, but we haven’t yet seen “any benefit in survival with the combo of chemotherapy and immunotherapy for resectable esophago-gastric cancer.”

Further studies are needed to evaluate the synergy of immunotherapy and radiotherapy. The next chapter of the esophageal adenocarcinoma story may feature a “best-of-both-worlds” approach that combines induction chemotherapy, followed by personalized chemoradiation, surgery, and potentially adjuvant immunotherapy, Dr. Goodman explained.

While the ESOPEC findings are impressive, the 5-year overall survival of only 50% is still suboptimal, she noted. “Given the poor prognosis with this disease, we need to continue to develop clinical trials to identify better targets, novel treatment combinations, and select patients that will respond best to specific treatment.”

ESOPEC was funded by the Deutsche Forschungsgemeinschaft (German Research Foundation). Dr. Hoeppner reported receiving travel, accommodations, and expenses from Intuitive Surgical. Dr. Goodman reported a relationship with the National Cancer Institute and consulting or advisory roles for Novartis, Philips Healthcare, RenovoRX, and Roche/Genentech.

A version of this article first appeared on Medscape.com.

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

Several new studies in lung cancer have opened their doors recently. Is one of your patients eligible to participate?

Resected stage II, IIIA, or IIIB with nodal involvement non–small cell lung cancer (NSCLC). Adult patients with this type of cancer can join a randomized, controlled, phase 3 study assessing whether an investigational drug called V940 added to pembrolizumab (Keytruda) delays cancer recurrence better than pembrolizumab alone.

V940 is an individualized neoantigen therapy designed to generate T-cell antitumor responses targeted to a patient’s specific mutation profile.

V940 plus pembrolizumab showed a trend toward longer recurrence-free survival vs pembrolizumab alone in a recent phase 2 study in melanoma (hazard ratio, 0.561; P = .053).

In the current trial, one group of participants will receive intramuscular injections of V940 every 3 weeks plus intravenous (IV) pembrolizumab every 6 weeks for up to approximately 1 year or until disease recurrence or unacceptable toxicity, whichever happens first. The other people in the trial will be on the same schedule, with a placebo replacing V940.

Centers in Florida, Georgia, Kentucky, Montana, New Jersey, New York, North Dakota, and six other countries started recruiting for the trial’s 868 participants in December 2023. Disease-free survival is the primary endpoint. Overall survival over approximately 12 years and quality of life (QoL) are secondary endpoints. More details at clinicaltrials.gov.

Metastatic NSCLC with a programmed cell death ligand 1 (PD-L1)–tumor proportion score of > 50%. Adults in this clinical situation are eligible for a randomized, open-label, phase 3 trial to determine whether an experimental antibody-drug conjugate called MK-2870 added to standard pembrolizumab prolongs survival.

MK-2870 delivers a cytotoxin to cancer cells by binding to trophoblast cell-surface antigen 2, known to promote tumor cell growth and metastasis. For up to 2 years, half of participants will receive MK-2870 by IV every 2 weeks plus IV pembrolizumab every 6 weeks. The other group will receive only pembrolizumab.

In December 2023, study sites in Georgia, Minnesota, Mississippi, Nevada, Oregon, Australia, Denmark, Taiwan, and Turkey started seeking the trial’s 614 participants. Overall survival over approximately 4 years is the primary endpoint; QoL is a secondary endpoint. More details at clinicaltrials.gov.

Untreated locally advanced or metastatic NSCLC with KRAS G12C mutations. Individuals with this type of lung cancer may be interested in a randomized, controlled, phase 3 study examining whether an experimental oral KRAS G12C inhibitor called LY3537982 boosts the effectiveness of standard treatment and patients can tolerate the combination. Currently approved KRAS G12C inhibitors sotorasib (Lumakras, Lumykras) and adagrasib (Krazati) are indicated for second-line treatment; this trial may lead to a first-line approval for newcomer LY3537982.

The trial has three parts: dose optimization, safety, and efficacy. During dose optimization, each participant will take one of two oral doses of LY3537982 and receive IV pembrolizumab every 3 weeks. In the safety phase, all participants will receive oral LY3537982 at the chosen dose plus standard therapy of 3-times-weekly IV pembrolizumab, pemetrexed, and a platinum therapy (cisplatin or carboplatin). In the experimental phase, for up to about 1 year, participants will receive one of these four options: Pembrolizumab plus LY3537982, pembrolizumab plus a placebo, standard therapy plus LY3537982, or standard therapy plus a placebo.

The study, which is planning to recruit 1016 participants, opened across 16 US states and 12 countries worldwide in December 2023. Sites in 11 more US states, the District of Columbia, Brazil, Canada, China, India, and 11 more European countries are gearing up. Adverse events and progression-free survival are the primary endpoints. Overall survival over approximately 3 years and QoL are secondary endpoints. More details at clinicaltrials.gov.

Unresectable, untreated locally advanced or metastatic non-squamous NSCLC with human epidermal growth factor receptor 2 (HER2) mutations. People with this diagnosis who have HER2 mutations instead of KRAS G12C mutations can participate in a phase 3 study comparing an investigational oral first-line treatment with standard IV therapy. The drug in this study, zongertinib, is a HER2 tyrosine kinase inhibitor.

For up to approximately 4 years, one group of participants will take oral zongertinib only, and the other individuals will receive IV pembrolizumab, pemetrexed, and a platinum agent (cisplatin or carboplatin). Study sites in California, Missouri, South Carolina, Australia, China, Japan, South Korea, and Singapore opened in January ready to welcome 270 participants. Progression-free survival is the primary outcome. Overall survival over 53 months and QoL are secondary endpoints. More details at clinicaltrials.gov.

Completely resected stage IIB, IIIA, or select IIIB, PD-L1–positive NSCLC. Adults with this type of lung cancer who have received adjuvant platinum-based chemotherapy may be eligible for a randomized, controlled, phase 3 study to assess whether two immune checkpoint inhibitors are better than one at delaying cancer recurrence. In this trial, tiragolumab will be added to the approved PD-L1 inhibitor atezolizumab (Tecentriq).

A recent study, however, found that tiragolumab did not confer an additional benefit when added to atezolizumab, carboplatin, and etoposide in untreated extensive-stage small cell lung cancer.

In the current trial, one group of participants will receive IV atezolizumab and tiragolumab, while the other people will receive a placebo instead of tiragolumab. Centers in California, Georgia, Illinois, New Mexico, Australia, China, South Korea, and Taiwan started recruiting for the trial’s 1150 participants in March 2024. Disease-free survival is the primary endpoint. Overall survival over approximately 15 years and QoL are secondary outcomes. More details at clinicaltrials.gov.

Previously treated metastatic or non-operable non-squamous NSCLC. Adults in this position who have received no more than one platinum-based chemotherapy and one anti–PD-L1 drug are sought for a randomized, open-label, phase 3 trial comparing second-line standard docetaxel with experimental antibody-drug conjugate sigvotatug vedotin. Patients who have tumors with certain treatable genomic alterations must have received at least one drug targeted to that alteration, as well as a platinum-based agent.

Approximately half the participants will receive sigvotatug vedotin by IV every 2 weeks, and the other half will receive IV docetaxel every 3 weeks. The study opened in March across 13 US states, France, Hungary, Poland, and Spain seeking 600 people eligible to participate. The primary outcomes are overall survival over approximately 5 years and objective response rate. QoL is a secondary outcome. More details at clinicaltrials.gov.All trial information is from the National Institutes of Health US National Library of Medicine (online at clinicaltrials.gov).

A version of this article appeared on Medscape.com .

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Andrew N. Wilner, MD: My guest today is Dr. Jose Merino, editor in chief of the Neurology family of journals and professor of neurology and co-vice chair of education at Georgetown University in Washington, DC.

Our program today is a follow-up of Dr. Merino’s presentation at the recent American Academy of Neurology meeting in Denver, Colorado. Along with two other panelists, Dr. Merino discussed the role of open-access publication and the dangers of predatory journals. 

Jose G. Merino, MD, MPhil: Thank you for having me here. It’s a pleasure.
 

Open Access Defined

Dr. Wilner: I remember when publication in neurology was pretty straightforward. It was either the green journal or the blue journal, but things have certainly changed. I think one topic that is not clear to everyone is this concept of open access. Could you define that for us? 

Dr. Merino: Sure. Open access is a mode of publication that fosters more open or accessible science. The idea of open access is that it combines two main elements. One is that the papers that are published become immediately available to anybody with an internet connection anywhere in the world without any restrictions. 

The second important element from open access, which makes it different from other models we can talk about, is the fact that the authors retain the copyright of their work, but they give the journal and readers a license to use, reproduce, and modify the content.

This is different, for example, from instances where we have funder mandates. For example, NIH papers have to become available 6 months after publication, so they’re available to everybody but not immediately. 

Then copyright is retained, in the case of NIH employees, for example, by the government or by the journals themselves. The two elements of open access, I think, are immediate access to the material and the fact that it’s published with a Creative Commons license. 

Dr. Wilner: I remember that when a journal article was published, say, in Neurology, if you didn’t have a subscription to Neurology, you went to the library that hopefully had a subscription.

If they didn’t have it, you would write to the author and say, “Hey, I heard you have this great paper because the abstract was out there. Could you send me a reprint?” Has that whole universe evaporated? 

Dr. Merino: It depends on how the paper is published. For example, in Neurology, some of the research we publish is open access. Basically, if you have an internet connection, you can access the paper.

That’s the case for papers published in our wholly open-access journals in the Neurology family like Neurology Neuroimmunology & Neuroinflammation, Neurology Genetics, or Neurology Education. 

For other papers that are published in Neurology, not under open access, there is a paywall. For some of them, the paywall comes down after a few months based on funder mandates and so on. As I was mentioning, the NIH-funded papers are available 6 months later. 

In the first 6 months, you may have to go to your library, and if your library has a subscription, you can download it directly. [This is also true for] those that always stay behind the paywall, where you have to have a subscription or your library has to have a subscription.
 

Is Pay to Publish a Red Flag?

Dr. Wilner: I’m a professional writer. With any luck, when I write something, I get paid to write it. There’s been a long tradition in academic medicine that when you submit an article to, say, Neurology, you don’t get paid as an author for the publication. Your reward is the honor of it being published. 

Neurology supports itself in various ways, including advertising and so on. That’s been the contract: free publication for work that merits it, and the journal survives on its own. 

With open access, one of the things that’s happened is that — and I’ve published open access myself — is that I get a notification that I need to pay to have my article that I’ve slaved over published. Explain that, please. 

Dr. Merino: This is the issue with open access. As I mentioned, the paper gets published. You’re giving the journal a license to publish it. You’re retaining the copyright of your work. That means that the journal cannot make money or support itself by just publishing open access because they belong to you. 

Typically, open-access journals are not in print and don’t have much in terms of advertising. The contract is you’re giving me a license to publish it, but it’s your journal, so you’re paying a fee for the journal expenses to basically produce your paper. That’s what’s happening with open access. 

That’s been recognized with many funders, for example, with NIH funding or many of the European funders, they’re including open-access fees as part of their funding for research. Now, of course, this doesn’t help if you’re not a funded researcher or if you’re a fellow who’s doing work and so on. 

Typically, most journals will have waived fees or lower fees for these situations. The reason for the open-access fee is the fact that you’re retaining the copyright. You’re not giving it to the journal who can then use it to generate its revenue for supporting itself, the editorial staff, and so on. 

Dr. Wilner: This idea of charging for publication has created a satellite business of what are called predatory journals. How does one know if the open-access journal that I’m submitting to is really just in the business of wanting my $300 or my $900 to get published? How do I know if that’s a reasonable place to publish? 
 

Predatory Journals

Dr. Merino: That’s a big challenge that has come with this whole idea of open access and the fact that now, many journals are online only, so you’re no longer seeing a physical copy. That has given rise to the predatory journals. 

The predatory journal, by definition, is a journal that claims to be open access. They’ll take your paper and publish it, but they don’t provide all the other services that you would typically expect from the fact that you’re paying an open-access fee. This includes getting appropriate peer review, production of the manuscript, and long-term curation and storage of the manuscript. 

Many predatory journals will take your open-access fee, accept any paper that you submit, regardless of the quality, because they’re charging the fees for that. They don’t send it to real peer review, and then in a few months, the journal disappears so there’s no way for anybody to actually find your paper anymore. 

There are certain checklists. Dr. David Moher at the University of Toronto has produced some work trying to help us identify predatory journals. 

One thing I typically suggest to people who ask me this question is: Have you ever heard of this journal before? Does the journal have a track record? How far back does the story of the journal go? Is it supported by a publisher that you know? Do you know anybody who has published there? Is it something you can easily access?

If in doubt, always ask your friendly medical librarian. There used to be lists that were kept in terms of predatory journals that were being constantly updated, but those had to be shut down. As far as I understand, there were legal issues in terms of how things got on that list. 

I think that overall, if you’ve heard of it, if it’s relevant, if it’s known in your field, and if your librarian knows it, it’s probably a good legitimate open-access journal. There are many very good legitimate open-access journals. 

I mentioned the two that we have in our family, but all the other major journals have their own open-access journal within their family. There are some, like BMC or PLOS, that are completely open-access and legitimate journals. 
 

Impact Factor

Dr. Wilner: What about impact factor? Many journals boast about their impact factor. I’m not sure how to interpret that number. 

Dr. Merino: Impact factor is very interesting. The impact factor was developed by medical librarians to try to identify the journals they should be subscribing to. It’s a measure of the average citations to an average paper in the journal. 

It doesn’t tell you about specific papers. It tells you, on average, how many of the papers in this journal get cited so many times. It’s calculated by the number of articles that were cited divided by the number of articles that were published. Journals that publish many papers, like Neurology, have a hard time bringing up their impact factor beyond a certain level. 

Similarly, very small journals with one or two very highly cited papers have a very high impact factor. It’s being used as a measure, perhaps inappropriately, of how good or how reputable a journal is. We all say we don’t care about journal impact factors, but we all know our journal impact factor and we used to know it to three decimals. Now, they changed the system, and there’s only one decimal point, which makes more sense. 

This is more important, for example, for authors when deciding where to submit papers. I know that in some countries, particularly in Europe, the impact factor of the journal where you publish has an impact on your promotion decisions. 

I would say what’s even more important than the impact factor, is to say, “Well, is this the journal that fits the scope of my paper? Is this the journal that reaches the audience that I want to reach when I write my paper?” 

There are some papers, for example, that are very influential. The impact factor just captures citations. There are some papers that are very influential that may not get cited very often. There may be papers that change clinical practice. 

If you read a paper that tells you that you should be changing how you treat your patients with myasthenia based on this paper, that may not get cited. It’s a very clinically focused paper, but it’s probably more impactful than one that gets cited very much in some respect, or they make it to public policy decisions, and so on. 

I think it’s important to look more at the audience and the journal scope when you submit your papers. 

Dr. Wilner: One other technical question. The journals also say they’re indexed in PubMed or Google Scholar. If I want to publish my paper and I want it indexed where the right people are going to find it, where does it need to be indexed? 

Dr. Merino: I grew up using Index Medicus, MedlinePlus, and the Library of Science. I still do. If I need to find something, I go to PubMed. Ideally, papers are listed in MedlinePlus or can be found in PubMed. They’re not the same thing, but you can find them through them. 

That would be an important thing. Nowadays, a lot more people are using Google Scholar or Google just to identify papers. It may be a little bit less relevant, but it’s still a measure of the quality of the journal before they get indexed in some of these. For example, if you get listed in MedlinePlus, it has gone through certain quality checks by the index itself to see whether they would accept the journal or not. That’s something you want to check.

Typically, most of the large journals or the journals you and I know about are listed in more than one place, right? They’re listed in Scopus and Web of Science. They’re listed in MedlinePlus and so on. Again, if you’re submitting your paper, go somewhere where you know the journal and you’ve heard about it. 

Dr. Wilner: I’m not going to ask you about artificial intelligence. We can do that another time. I want to ask something closer to me, which is this question of publish or perish. 

There seems to be, in academics, more emphasis on the number of papers that one has published rather than their quality. How does a younger academician or one who really needs to publish cope with that? 

Dr. Merino: Many people are writing up research that may not be relevant or that may not be high quality just because you need to have a long list of papers to get promoted, for example, if you’re an academician. 

Doug Altman, who was a very influential person in the field quality of not only medical statistics but also medical publishing, had the idea that we need less research, but we need better research. 

We often receive papers where you say, well, what’s the rationale behind the question in this paper? It’s like they had a large amount of data and were trying to squeeze as much as they could out of that. I think, as a young academician, the important thing to think about is whether it is an important question that matters to you and to the field, from whatever perspective, whether it’s going to advance research, advance clinical care, or have public policy implications. 

Is this one where the answer will be important no matter what the answer is? If you’re thinking of that, your work will be well recognized, people will know you, and you’ll get invited to collaborate. I think that’s the most important thing rather than just churning out a large number of papers. 

The productivity will come from the fact that you start by saying, let me ask something that’s really meaningful to me and to the field, with a good question and using strong research methodology. 

Dr. Wilner: Thanks for that, Dr. Merino. I think that’s very valuable for all of us. This has been a great discussion. Do you have any final comments before we wrap up? 

Dr. Merino: I want to encourage people to continue reading medical journals all the time and submitting to us, again, good research and important questions with robust methodology. That’s what we’re looking for in Neurology and most serious medical journals.
 

Dr. Wilner is an associate professor of neurology at the University of Tennessee Health Science Center, Memphis. Dr. Merino is a professor in the department of neurology at Georgetown University Medical Center, Washington, DC. Dr. Wilner reported conflicts of interest with Accordant Health Services and Lulu Publishing. Dr. Merino reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

A version of this article first appeared on Medscape.com.

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

A version of this article first appeared on Medscape.com.

CHICAGO — Adding carboplatin to standard anthracycline/taxane treatment for early-stage triple-negative breast cancer (TNBC) improves event-free and overall survival in the neoadjuvant and adjuvant setting, according to a phase 3 trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The outcomes of the South Korean study, dubbed PEARLY, provide strong evidence for incorporating carboplatin into both the neoadjuvant and adjuvant settings in patients with early-stage TNBC, said lead investigator and presenter Joohyuk Sohn, MD, PhD, a medical oncologist at Yonsei University, Seoul, South Korea.

In early-stage TNBC, carboplatin is already being incorporated into the neoadjuvant setting on the basis of trial results from KEYNOTE-522 that demonstrated improved pathologic complete response rates and event-free survival with the platinum alongside pembrolizumab.

However, the overall survival benefit of carboplatin in this setting remains unclear, as does the benefit of platinum add-on in the adjuvant setting, Dr. Sohn explained.

Dr. Sohn and colleagues randomized 868 patients evenly to either standard treatment — doxorubicin, anthracycline, and cyclophosphamide followed by a taxane — or an experimental arm that added carboplatin to the taxane phase of treatment.

About 30% of women were treated in the adjuvant setting, the rest in the neoadjuvant setting. The two arms of the study were generally well balanced — about 80% of patients had stage II disease, half were node negative, and 11% had deleterious germline mutations.

The primary endpoint, event-free survival, was broadly defined. Events included disease progression, local or distant recurrence, occurrence of a second primary cancer, inoperable status after neoadjuvant therapy, or death from any cause.

Adding carboplatin increased 5-year event-free survival rates from 75.1% to 82.3% (hazard ratio [HR], 0.67; P = .012) with the benefit holding across various subgroup analyses and particularly strong for adjuvant carboplatin (HR, 0.26).

Five-year overall survival was also better in the carboplatin arm — 90.7% vs 87% in the control arm (HR, 0.65; 95% CI, 0.42-1.02) — but that benefit did not reach statistical significance (P = .057)

Invasive disease-free survival (HR, 0.73) and distant recurrence-free survival (HR, 0.77) favored carboplatin, but the results also weren’t statistically significant.

Overall, 46% of patients had a pathologic complete response with carboplatin vs nearly 40% in the control arm. The pathologic complete response benefit from carboplatin add-on was consistent with past reports.

As expected, adding carboplatin to treatment increased hematologic toxicity and other adverse events, with three-quarters of patients experiencing grade 3 or worse adverse events vs 56.7% of control participants. There was one death in the carboplatin arm from pneumonia and two in the control arm — one from septic shock and the other from suicide.

Dr. Sohn and colleagues, however, did not observe a quality of life difference between the two groups.

“The PEARLY trial provides compelling evidence for including carboplatin in the treatment of early-stage TNBC,” Dr. Sohn concluded, adding that the results underscore the benefit in the neoadjuvant setting and suggest “potential applicability in the adjuvant setting post surgery.”

Study discussant Javier Cortes, MD, PhD, believes that the PEARLY provides a strong signal for adding carboplatin in the adjuvant setting.

“That’s something I would do in my clinical practice,” said Dr. Cortes, head of the International Breast Cancer Center in Barcelona, Spain. “After ASCO this year, I would offer taxanes plus carboplatin following anthracyclines.”

An audience member, William Sikov, MD, a breast cancer specialist at Brown University in Providence, Rhode Island, said he hopes “we’ve reached the end of a road that started many years ago in terms of incorporating carboplatin as part of neoadjuvant and adjuvant therapy for triple-negative breast cancer, where we finally [reach] consensus that this is necessary in our triple-negative patients.”

The work was funded by the government of South Korea and others. Dr. Sohn reported stock in Daiichi Sankyo and research funding from Daiichi and other companies. Dr. Cortes disclosed numerous industry ties, including honoraria, research funding, and/or travel expenses from AstraZeneca, Daiichi, and others.

A version of this article first appeared on Medscape.com.