Conference Coverage

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

COPENHAGEN – European recommendations and overarching principles for the management of patients with axial spondyloarthritis (axSpA) have remained largely unchanged since 2016 – with a few notable but very important exceptions.

The 2022 updated recommendations include a new point regarding which biologic agents to use for patients with recurrent uveitis, active inflammatory bowel disease (IBD), or significant psoriasis, as well as new advice to reevaluate the diagnosis and consider the presence of comorbidities if the disease doesn’t respond to current therapies, reported Sofia Ramiro, MD, PhD, from Leiden (Netherlands) University Medical Center.

She summarized the 2022 updates at the annual European Congress of Rheumatology on behalf of colleagues in the ASAS (Assessment of SpondyloArthritis International Society)/EULAR committee.

Among other significant updates are a recommendation for managing patients with persistently high disease activity despite conventional therapy, and a recommendation as to what to do when a first biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) fails, Dr. Ramiro said at the meeting.

“Although we have more changes in the pharmacological part, I would like to emphasize the importance of nonpharmacological treatment in axial SpA,” she said.

Overarching principles

The members of the committee that created the recommendations were in complete agreement that axSpA, as they state in the overarching principles, “is a potentially severe disease with diverse manifestations, usually requiring multidisciplinary management coordinated by the rheumatologist.”

They also universally acknowledged that “the primary goal of treating the patient with axSpA is to maximize health-related quality of life through control of symptoms and inflammation, prevention of progressive structural damage, preservation/normalization of function, and social participation.”

The overarching principles include the aforementioned emphasis on both pharmacologic and nonpharmacologic management, shared decision-making between patients and rheumatologists, and awareness of the potential financial toxicities and societal problems that patients face.

A closer look: New recommendations

As noted before, there are two new recommendations since the 2016 iteration.

Recommendation No. 10 states, “If there is a history of recurrent uveitis or active IBD, preference should be given to a monoclonal antibody against TNF-alpha [tumor necrosis factor–alpha]. For patients with significant psoriasis, an IL-17 [interleukin-17] inhibitor may be preferred.”

This recommendation stipulates that it refers only to IL-17A inhibitors.

The other new recommendation, No. 11, seems like plain common sense. It states, “Absence of response to treatment should trigger reevaluation of the diagnosis and consideration of the presence of comorbidities.”

Revised recommendations

The two significantly revised recommendations deal with drug therapy.

Recommendation No. 9 holds that for patients with persistently high disease activity despite conventional therapy, a TNF inhibitor, including the pegylated humanized antigen-binding fragment certolizumab pegol (Cimzia), an IL-17 inhibitor, or Janus kinase (JAK) inhibitor, should be considered.

Recommendation No. 12 states that if the first biologic or targeted synthetic DMARD fails, switching to another biologic DMARD (TNF inhibitor or IL-17 inhibitor) or JAK inhibitor should be considered.

Transatlantic similarities, differences

Lianne Gensler, MD, a rheumatologist and professor of medicine at the University of California, San Francisco, who served on the committee that developed the 2019 American College of Rheumatology guidelines for the treatment of ankylosing spondylitis and nonradiographic axSpA, said that, while there are similarities between some of the recommendations promulgated on each side of the Atlantic, there are significant differences and even opposing viewpoints.

A primary difference between the two is the methodology used to arrive at the recommendations in the first place, she said in an interview with this news organization.

“ACR uses a very robust approach to guideline development, where each question is addressed by a ‘PICO’ ” population, intervention, control, and outcomes – and that’s good if you have good evidence, but sometimes – often, in fact – we don’t have strong evidence that would lead everyone to choose the same approach every time, and that’s true especially in inflammatory arthritis, where there’s a lot of shared decision-making, so many of the recommendations out of ACR are conditional,” she said.

In contrast, the ASAS/EULAR recommendations are based largely on broader levels of evidence and on consensus. In developing the European recommendations, the authors were able to take into account drugs that were newly approved since the 2019 ACR guidelines were issued, she noted.

Although many of the broader recommendations are similar, they diverge when it comes to specific issues, such as whether to treat to target.

“ACR guidelines say, ‘Do not treat to target.’ EULAR guidelines say it’s okay to treat to target. ACR guidelines made that decision because at that time, there was no treat-to-target data,” Dr, Gensler said.

“I think, as rheumatologists, we always want to aim for a goal in a patient, so it’s not unreasonable, but I think we shouldn’t attach too much to a number,” she said.

Another difference is that the ACR guidelines recommend against switching to a biosimilar agent when a patient’s condition is stable with the originator biologic.

Dr. Gensler said that she particularly appreciated the new EULAR recommendation (No. 11) to reconsider the diagnosis for patients for whom therapies have failed.

“The sense that nonresponse means ongoing disease activity and therefore drug escalation or change needs to happen is not always the right answer,” she said.

The process for developing the recommendations was supported by EULAR. Dr. Ramiro has received research grants and consulting and/or speaking fees from AbbVie, Eli Lilly, Galapagos, Merck Sharp and Dohme, Novartis, Pfizer, Sanofi, and UCB. Dr. Gensler has received research grant support from Novartis, Pfizer, and UCB and has consulting relationships with AbbVie, Gilead, Janssen, MoonLake, Novartis, and Pfizer.

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

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- Breast cancer patients with low levels of HER2 expression, previously considered untreatable with HER2-targeted therapies, benefited from the anti-HER2 antibody drug conjugate trastuzumab deruxtecan. The therapy doubled progression-free survival versus chemotherapy in patients with hormone receptor positive (HR+) and low levels of HER2.

“Overall, these results establish HER2 low metastatic breast cancer as a targetable population of breast cancer with trastuzumab deruxtecan as a new standard of care in this setting,” said Shanu Modi, MD, during a press conference held in Chicago at the annual meeting of the American Society of Clinical Oncology, where she presented the results.

“I think the results of this trial clearly will be practice changing,” said ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, during the press conference. “I think what this trial does is really extend the benefits of this agent to a whole new group of patients that traditionally is really quite difficult to treat. I think this will offer a wonderful new option for patients and also will really fundamentally change the way we think about HER2 status and how we classify this in our metastatic patients,” Dr. Meisel added.

The conjugate includes the anti-HER2 antibody trastuzumab and the topoisomerase I inhibitor deruxtecan, which interferes with DNA replication. Trastuzumab has demonstrated efficacy in patients with high levels of HER2 expression, and trastuzumab-deruxtecan received FDA approval in May 2022 for the treatment of HER2-positive breast cancer in patients who had previously received an anti-HER2 regimen.

However, anti-HER2 agents had not been shown to benefit HER2-low patients, defined as immunohistochemistry (IHC) 1+ or 2+. About 60% of breast cancer patients traditionally thought of HER2 negative could be classified as HER2 low, according to Dr. Modi, who is a medical oncologist at Memorial Sloan Kettering Cancer Center, New York.

Asked why she thought trastuzumab deruxtecan succeeded where other anti-HER2 therapies failed in this population, Dr. Modi highlighted the nature of the drug conjugate, including a high drug payload and the use of a topoisomerase inhibitor, which is rarely employed against breast cancer. Once released from the antibody, the drug retains its ability to cross cell membranes and enter the tumor microenvironment. That ‘knock on’ effect might allow it to reach neighboring cells that don’t express HER2. “We know HER2 expression is very heterogeneous. I think that’s why, for the first time, we’re seeing activity for a targeted agent,” Dr. Modi said.

The DESTINY-Breast04 study included 557 patients in Asia, Europe, and North America with HR-negative or HR-positive, HER2-low, unresectable, and/or metastatic breast cancer. Patients were randomized to trastuzumab deruxtecan or physician’s choice of several standard chemotherapy drugs. After a median follow-up of 18.4 months, compared with the chemotherapy group, patients in the trastuzumab deruxtecan arm had a 49% reduction in risk of progression and a 36% reduction in mortality. The group also had longer progression-free survival (10.1 months vs. 5.4 months) and overall survival (23.9 months vs. 17.5 months).

Although adverse events were similar between the two groups (52.6% in trastuzumab deruxtecan, 67.4% in chemotherapy), lung toxicity occurred in 12% of the group, and there were 3 fatalities as a result (0.8%). Interstitial lung disease/pneumonitis has been linked to trastuzumab treatment in the past, with one meta-analysis finding a frequency of 2.4% and fatality rate of 0.2%.

Additional studies are in progress to determine the minimum threshold of HER2 expression needed to gain a benefit from trastuzumab deruxtecan treatment.

The study was funded by Daiichi Sankyo, and AstraZeneca. Dr. Modi has advised, consulted for, or received honoraria from Daiichi Sankyo, and AstraZeneca. Dr. Meisel has advised or consulted for Medscape and AstraZeneca.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- An antibody drug conjugate that targets a cell-surface antigen found on most breast and bladder cancers demonstrated improved progression-free survival over standard chemotherapy in patients with endocrine-resistant hormone receptor positive/HER2 negative metastatic breast cancer.

The agent, called sacituzumab govitecan (Trodelvy, Gilead), was approved on an accelerated basis in 2020 by the Food and Drug Administration for patients with unresectable locally advanced or metastatic triple-negative breast cancer. It received regular approval in 2021.

The conjugate includes an antibody that targets the Trop-2 protein. The antibody is bound to govitecan, which is the active metabolite of the topoisomerase inhibitor 1 irinotecan.

“Sacituzumab demonstrated significant and clinically meaningful benefit, compared with chemotherapy in patients with heavily pretreated endocrine resistant hormone receptor positive, HER2 negative, advanced breast cancer and should be considered a potential treatment in this heavily pretreated patient population,” said lead author Hope S. Rugo, MD, during a press conference held June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology. Dr. Rugo is director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco comprehensive cancer center.

The results drew praise from ASCO spokesperson and breast cancer expert Jane Lowe Meisel, MD, since patients with HR+/HER2- metastatic breast cancer who become resistant to endocrine therapy are left with only sequential, single-agent chemotherapy. “We’ve all been eagerly awaiting the results of this trial. These estrogen positive endocrine negative resistant patients really are an area of great unmet clinical need, and their cancers can be very difficult to treat,” Dr. Meisel said during the press conference.

Approximately, 74% of all breast cancers are HR positive/HER2 negative. And, of these, 92% of patients live beyond five years, according to the American Cancer Society.

The study found a relatively small 1.5 months difference in median progression-free survival, but the results are nevertheless clinically important, especially given that 21% of patients were progression-free at one year, compared with 7% in the chemotherapy arm. “When you look at the patients who do respond on sacituzumab govitecan, it seems that they tend to respond better and longer. The idea that someone with such heavily pretreated disease could walk into your clinic and you could offer them an option that would allow them a one in five chance of still not having progressed at one year is really huge from a clinical standpoint,” Dr. Meisel said.

“This is what we need, incremental options that may be different or better than chemotherapy, so I think this really represents a step forward for the field,” he said.

Two other antibody-drug conjugates that are FDA approved for HER2-positive breast cancer include ado-trastuzumab emtansine (Kadcyla, Genentech) and fam-trastuzumab deruxtecan (Enhertu, AstraZeneca, and Daiichi Sankyo). This new wave of therapies is exciting, according to Julie Gralow, MD, who is chief medical officer and executive vice president of ASCO. “I think this way of delivering chemotherapy inside the cancer cell by having an antibody directed to something on the cell surface and then internalization is really, really very interesting,” Dr. Gralow said during the press conference.

The study included 543 patients from 113 international centers who had previously received endocrine therapy, CDK4/6 inhibitors, and at least two previous regimens of chemotherapy. Median progression-free survival (PFS) was 5.5 months in the sacituzumab govitecan group and 4.0 months in the chemotherapy group (hazard ratio, 0.66; P <.001). PFS was more frequent at 6 months (46% vs. 30%) and 12 months (21% vs. 7%). There was no significant improvement in overall survival (13.9 months vs. 12.3 months). The sacituzumab govitecan group had higher rates of overall response (21% vs. 14%) and clinical benefit (34% vs. 22%), as well as a longer median duration of response (7.4 vs. 5.6 months).

Adverse events were more common with sacituzumab govitecan (74% vs. 60%), including low white blood cell counts (51% vs. 39%) and diarrhea (10% vs. 1%). Both groups had low rates of treatment discontinuation due to adverse events (6% in sacituzumab govitecan vs. 4% in chemotherapy).

Dr. Rugo has received honoraria from Puma Biotechnology and Samsung Bioepis, has consulted for Napo Pharmaceuticals, and has received funding from Astellas Pharma, AstraZeneca, Ayala Pharmaceuticals, Daiichi Sankyo, Genentech, Gilead Sciences, Lilly, Merck, Novartis, OBI Pharma, Odonate Therapeutics, Pfizer, and Sermonix Pharmaceuticals. Dr. Meisel has advised or consulted for Medscape and Total Health Conferencing. She has advised or consulted for AstraZeneca, Curio Science, Genentech, GlaxoSmithKline, Novartis, and SeaGen. She has received research funding from Pfizer and Seattle Genetics. She has received travel, accommodation, or expenses from Pfizer, Puma Biotechnology, and Total Health Conferencing.

CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.

The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.

The study was simultaneously published online in the Journal of Clinical Oncology.

Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.

Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.

“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.

The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.

For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.

A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.

A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.

Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.

Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.

CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.

The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.

The study was simultaneously published online in the Journal of Clinical Oncology.

Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.

Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.

“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.

The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.

For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.

A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.

A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.

Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.

Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.

CHICAGO -- Circulating tumor DNA successfully identified minimal residual disease in patients with hormone receptor-positive (HR+) breast cancer who are at high risk for recurrence – generally years before metastases occurs. The findings come from the CHiRP study, which included patients who were at least 5 years post diagnosis.

The researchers and other groups previously showed that minimal residual disease (MRD) status is associated with distant-recurrence free survival, “yet little is known about ctDNA in the late adjuvant setting in hormone receptor-positive breast cancer,” said Marla Lipsyc-Sharf, MD, a clinical fellow in medicine at Dana-Farber Cancer Institute, Boston. Dr. Lipsyc-Sharf presented her findings June 4 in Chicago at the annual meeting of the American Society of Clinical Oncology.

The study was simultaneously published online in the Journal of Clinical Oncology.

Plasma samples were collected at follow-up visits every 6-12 months, and a personalized version of the RaDaR assay was used to detect ctDNA associated with MRD. Although the technology is currently only useful for research, the team hopes it can soon provide clinical guidance. “The CHiRP study is an important first step toward an understanding of the baseline prevalence and role of ctDNA in this setting. Multiple prospective clinical trials are underway or beginning to establish the clinical utility of ctDNA assays in this setting and understand whether intervention after MRD detection improves patient outcomes, such as survival or quality of life,” she said.

Ben Ho Park, MD, PhD, an oncologist with Vanderbilt University Medical Center, Nashville, Tenn., described the findings as encouraging.

“I think most of us saw this very striking data that you could actually predict who’s going to recur and that all patients who did recur were ctDNA positive. The numbers are really, indeed very encouraging that we can develop assays now that detect minimal residual disease with serum monitoring. It really opens up the floodgates for designing studies [to determine] who to treat with additional adjuvant therapies while they’re still in the adjuvant phase of breast cancer therapy,” Dr. Park said during a discussion that followed the presentation.

The study included 83 patients with high-risk HR+ breast cancer and no evidence of recurrence within 5 years of diagnosis. High risk was defined as T3/T4 and/or N2/N3 disease; T1/N1 disease with 3 or more lymph nodes involved; or T2N1 disease with Ki67 ≥ 20%, grade 3, or oncotype DX score ≥ 26.

For each patient, clinicians designed a tumor-informed liquid biopsy assay to detect plasma ctDNA. A total of 68.7% of participants had stage 3 disease. A total of 90.4% received curative-intent chemotherapy, and all received endocrine therapy. A total of 47% remained on endocrine therapy at their last follow-up.

A total of 93.2% of patients who completed adjuvant endocrine therapy had at least 5 years of treatment. A median of 8.4 years elapsed between diagnosis and first ctDNA sample, and the median follow-up was 10.4 years from diagnosis and 1.8 years from the first sample.

A total of 5% of patients had MRD when they entered the study, and 10% were found to have MRD at any time. Of 6 patients (7.2%) who experienced a metastatic recurrence, all were MRD+, and ctDNA evidence appeared as soon as 37.6 months before diagnosis (median 12.4 months). Of eight patients who were MRD+ at some point, two of them had not had a recurrence at the latest follow-up, and one patient had no follow-up at all, and the other had a follow-up 15.4 months after ctDNA detection.

Limitations of the study included a limited follow-up period and low rate of recurrence, as well as infrequent plasma sampling.

Dr. Lipsyc-Sharf has no relevant financial disclosures. Dr. Park has financial relationships and/or has received funding from Celcuity, Loxo, Casdin Capital, EQRx, Guardant Health, Hologic, Horizon Discovery, Jackson Laboratory for Genomic Medicine, Sermonix Pharmaceuticals, Abbvie, GE Healthcare, Lilly, Pfizer, Horizon Discovery, and Tempus.

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

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

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

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

COPENHAGEN – Here’s reassuring news for pregnant women with rheumatic diseases treated with tumor necrosis factor (TNF)–alpha inhibitors: Although the drugs vary widely in their transmissibility across the placenta, there appears to be no excess risk for serious infections in children exposed in utero to TNF inhibitors with high, compared with low, placental transfer.

That’s according to investigators at McGill University in Montreal, who studied outcomes for nearly 3,000 infants who were exposed to TNF inhibitors during gestation.

“Our data are reassuring as we saw no strong signal, which suggests that there is no need to switch the mother’s drugs. More studies are needed, but this is a step in the right direction to reduce maternal stress and reassure physicians,” said Leah K. Flatman, MSc, a PhD candidate in epidemiology at McGill.

Ms. Flatman presented the findings in an oral abstract session at the annual European Congress of Rheumatology.

Not without risks

Approximately 20% of pregnant women with chronic inflammatory diseases are prescribed a TNF inhibitor, a class of drug that is effective for disease control but also increases risk for infection because of immunosuppressive effects.

“Similarly, offspring exposed in utero to TNF inhibitors may also experience immunosuppression and subsequent serious infections in their first year of life. This is the result of the TNF inhibitor entering the fetal bloodstream at different concentrations,» Ms. Flatman said.

Anti-TNF monoclonal immunoglobulins, such as infliximab (Remicade and biosimilars), adalimumab (Humira and biosimilars), and golimumab (Simponi) have the highest placental transfer, reaching higher levels in fetal circulation than in maternal circulation, she noted.

In contrast, certolizumab (Cimzia), a pegylated humanized antigen-binding fragment, and etanercept (Enbrel and biosimilars), a fusion protein, have the lowest placental penetration, Ms. Flatman said.

Population study

The investigators conducted a population cohort study using the IBM MarketScan database of commercial claims from employer-provided health insurance plans in the United States.

They looked at data on offspring of mothers with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and/or inflammatory bowel diseases (IBD; Crohn’s disease, and ulcerative colitis). The children were born from Jan. 1, 2011 through Dec. 31, 2019.

The exposure was at least one filled prescription and/or infusion procedure claim for TNF inhibitors in the 6 months before delivery. The exposures were divided into high and low placental-transfer categories.

A total of 26,088 offspring were identified, of whom 2,902 (11.1%) were exposed to a TNF inhibitor in utero. A little more than half of these children were born to mothers treated with TNF inhibitors for IBD.

For the primary outcome of serious infections (based on at least one hospitalization with infection in the first year of life), the investigators plotted Kaplan-Meier curves, which showed that the survival probability of serious infections in the high and low groups overlapped, indicating no large differences.

Of 2,105 offspring of mothers treated with a high–placental-transfer drug, 38 (1.8%) had serious infections, compared with 10 of 797 offspring (1.3%) of mothers who received low–placental-transfer drugs.

In multivariable analysis that controlled for maternal age at delivery, any RA diagnosis without an IBD diagnosis, and IBD diagnosis, gestational or pregestational diabetes, maternal asthma, preterm delivery, corticosteroid use, and disease-modifying antirheumatic drug use, the investigators saw that the hazard ratio for risk for serious infection in the high–, compared with the low–placental-transfer group was 1.20, with a confidence interval crossing 1, indicating nonsignificance.

Similar results reported

Frauke Förger, MD, professor of rheumatology and immunology at the University of Bern (Switzerland), who comoderated the oral abstract session where the data were presented, told this news organization that the findings were in line with those of a recent meta-analysis looking at the safety of biologic agents in pregnant women with IBD.

She added, however, that although the meta-analysis also showed little difference in outcomes for the children of women treated with high– compared with low–placental-transfer drugs, “we need more data to be sure about this.”

Comoderator Gabriela Riemekasten, MD, director of the clinic for rheumatology and clinical immunology at University Hospital in Lübeck, Germany, told this news organization that she was surprised to see that more women received high– than low–placental-transfer drugs.

Although there was a 20% difference between the groups, the numbers were relatively low, and “I would consider this in my practice and give my patients the advice of these data,” she said.

The study was supported by an Arthritis Society PhD Salary Award, and a Canadian Institutes of Health Project grant. Ms. Flatman, Dr. Förger, and Dr. Riemekasten reported having no relevant financial disclosures.

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

COPENHAGEN – Baricitinib (Olumiant), a Janus kinase (JAK) inhibitor, significantly increases time to disease flare and decreases frequency of flares in patients with juvenile idiopathic arthritis (JIA), according to the results of a phase 3, placebo-controlled study.

The results support use of baricitinib when biologic or conventional synthetic disease-modifying antirheumatic drugs (DMARDs) fail.

 The difference in the proportion of patients who flared between baricitinib and placebo was seen as soon as 4 weeks after half of the patients switched from active drug to placebo, at 3.7% versus 23.5% respectively, reported Athimalaipet Ramanan, MD, from the University of Bristol (England) who presented the findings of the withdrawal, efficacy, and safety study at the annual European Congress of Rheumatology.

  “Our patients and parents have been waiting for alternative drugs for JIA, so JAK inhibitors have come at the right time,” he said. “These are really very encouraging findings for families, caregivers, and patients with JIA, to have an effective oral JAK inhibitor for managing these children.”

 In reporting the key findings, Dr. Ramanan added that the majority of patients (76%) achieved a JIA-ACR (American College of Rheumatology) 30 score during the 12-week open-label phase and went on to enter the double-blind withdrawal phase of the trial.

 Baricitinib 2-mg tablets are already Food and Drug Administration approved for the treatment of adults with moderately to severely active rheumatoid arthritis. This study, sponsored by the drug manufacturer Eli Lilly, aimed to investigate the efficacy and safety in pediatric patients with JIA who have shown an inadequate response to conventional synthetic or biologic DMARDs.

“For juvenile patients we need to make a dose adjustment [from the adult dosing], especially because we don’t have long-term safety data from JAK inhibitors in general,” said Osama Elfayad, MD, rheumatologist from Mouwasat Hospital, Dammam, Saudi Arabia who attended the presentation and commented on the findings.

He emphasized that safety was of primary concern in the pediatric population who have a long life expectancy. “For me it is essential to have good long-term safety data in juvenile patients. If we start with 4 mg and if the patient is controlled, we should shift to 2 mg which will be much better. I understand some clinicians are asking for 1 mg.”

Study details

The study population included patients aged from 2 to 17 years old with extended oligo- or polyarticular JIA, enthesitis-related juvenile idiopathic arthritis (ERA) and juvenile psoriatic arthritis.

 The trial was divided into three periods: a 2-week safety assessment, a 12-week open-label lead-in phase, and an up-to 32-week double-blind withdrawal phase. After confirmation of dose and safety, children were enrolled in the open-label phase receiving age-based, oral, once daily doses of baricitinib.

 “The primary endpoint is really concerned with the next phase of the study [double-blind withdrawal phase] looking at the proportion of patients who have shown a response at week 12 [achieved JIA-ACR30] but when switched from active drug to placebo have a flare,” explained Dr. Ramanan.

Patients were randomized 1:1 to continuing baricitinib or newly starting placebo until disease flare or up to week 32. The time to flare during the double-blind phase was the primary endpoint, while secondary endpoints included JIA-ACR30/50/70/90 response rates at week 12, and the proportion of patients with a flare during the double-blind phase.

 “These secondary endpoints are more relevant to the clinic,” noted Dr. Ramanan.

 A total of 219 patients entered the open-label phase, and of these, 163 achieved a JIA-ACR 30. These 163 children entered the double-blind stage and were randomized to baricitinib four times a day (56 completed), or placebo (32 completed).

 Two-thirds of patients were female, which is typical of the disease, explained Dr. Ramanan, and over two-thirds were White. “Most patients had had disease for around 4 years, and about half had had prior biologic therapy. About half were on baseline methotrexate and almost one-third had used corticosteroids although at doses of under 0.2mg/kg.

“It’s gratifying to see that over 75% achieved a JIA-ACR 30 [76.3%]. More importantly, two-thirds of the patients have a JIA-ACR 50 [63.5%], and almost half of the patients have a JIA-ACR 70 [46.1%]. This is pretty significant at 12 weeks only,” he remarked.

The key finding, however, was in the withdrawal phase, said Dr. Ramanan. “We see that those patients who had a response at week 12 and were then switched to placebo, about half [50.6%] flared on placebo, compared to only 17% of those who continued with baricitinib. So not only do those who switch to placebo have a higher frequency of flares but they are more likely to flare quickly, as early as 4 weeks.”

With respect to safety, he said: “This shows short-term safety, but what we really need is medium and long-term safety data. It is no surprise that most of the events seen were as expected in children including nasopharyngitis, upper respiratory tract infections, and nausea.”  

In the baricitinib versus placebo phase, 4.9% had serious adverse events in the baricitinib group compared to 3.7% in the placebo group. “There was nothing we didn’t expect to see which was mainly infection,” said Dr. Ramanan.

Dr. Elfayad has no disclosures. Professor Ramanan is a consultant for Eli Lilly, Abbvie, Roche, UCB, Novartis, Pfizer, and Sobi. He has received grant/research support from Eli Lilly.

COPENHAGEN – Baricitinib (Olumiant), a Janus kinase (JAK) inhibitor, significantly increases time to disease flare and decreases frequency of flares in patients with juvenile idiopathic arthritis (JIA), according to the results of a phase 3, placebo-controlled study.

The results support use of baricitinib when biologic or conventional synthetic disease-modifying antirheumatic drugs (DMARDs) fail.

 The difference in the proportion of patients who flared between baricitinib and placebo was seen as soon as 4 weeks after half of the patients switched from active drug to placebo, at 3.7% versus 23.5% respectively, reported Athimalaipet Ramanan, MD, from the University of Bristol (England) who presented the findings of the withdrawal, efficacy, and safety study at the annual European Congress of Rheumatology.

  “Our patients and parents have been waiting for alternative drugs for JIA, so JAK inhibitors have come at the right time,” he said. “These are really very encouraging findings for families, caregivers, and patients with JIA, to have an effective oral JAK inhibitor for managing these children.”

 In reporting the key findings, Dr. Ramanan added that the majority of patients (76%) achieved a JIA-ACR (American College of Rheumatology) 30 score during the 12-week open-label phase and went on to enter the double-blind withdrawal phase of the trial.

 Baricitinib 2-mg tablets are already Food and Drug Administration approved for the treatment of adults with moderately to severely active rheumatoid arthritis. This study, sponsored by the drug manufacturer Eli Lilly, aimed to investigate the efficacy and safety in pediatric patients with JIA who have shown an inadequate response to conventional synthetic or biologic DMARDs.

“For juvenile patients we need to make a dose adjustment [from the adult dosing], especially because we don’t have long-term safety data from JAK inhibitors in general,” said Osama Elfayad, MD, rheumatologist from Mouwasat Hospital, Dammam, Saudi Arabia who attended the presentation and commented on the findings.

He emphasized that safety was of primary concern in the pediatric population who have a long life expectancy. “For me it is essential to have good long-term safety data in juvenile patients. If we start with 4 mg and if the patient is controlled, we should shift to 2 mg which will be much better. I understand some clinicians are asking for 1 mg.”

Study details

The study population included patients aged from 2 to 17 years old with extended oligo- or polyarticular JIA, enthesitis-related juvenile idiopathic arthritis (ERA) and juvenile psoriatic arthritis.

 The trial was divided into three periods: a 2-week safety assessment, a 12-week open-label lead-in phase, and an up-to 32-week double-blind withdrawal phase. After confirmation of dose and safety, children were enrolled in the open-label phase receiving age-based, oral, once daily doses of baricitinib.

 “The primary endpoint is really concerned with the next phase of the study [double-blind withdrawal phase] looking at the proportion of patients who have shown a response at week 12 [achieved JIA-ACR30] but when switched from active drug to placebo have a flare,” explained Dr. Ramanan.

Patients were randomized 1:1 to continuing baricitinib or newly starting placebo until disease flare or up to week 32. The time to flare during the double-blind phase was the primary endpoint, while secondary endpoints included JIA-ACR30/50/70/90 response rates at week 12, and the proportion of patients with a flare during the double-blind phase.

 “These secondary endpoints are more relevant to the clinic,” noted Dr. Ramanan.

 A total of 219 patients entered the open-label phase, and of these, 163 achieved a JIA-ACR 30. These 163 children entered the double-blind stage and were randomized to baricitinib four times a day (56 completed), or placebo (32 completed).

 Two-thirds of patients were female, which is typical of the disease, explained Dr. Ramanan, and over two-thirds were White. “Most patients had had disease for around 4 years, and about half had had prior biologic therapy. About half were on baseline methotrexate and almost one-third had used corticosteroids although at doses of under 0.2mg/kg.

“It’s gratifying to see that over 75% achieved a JIA-ACR 30 [76.3%]. More importantly, two-thirds of the patients have a JIA-ACR 50 [63.5%], and almost half of the patients have a JIA-ACR 70 [46.1%]. This is pretty significant at 12 weeks only,” he remarked.

The key finding, however, was in the withdrawal phase, said Dr. Ramanan. “We see that those patients who had a response at week 12 and were then switched to placebo, about half [50.6%] flared on placebo, compared to only 17% of those who continued with baricitinib. So not only do those who switch to placebo have a higher frequency of flares but they are more likely to flare quickly, as early as 4 weeks.”

With respect to safety, he said: “This shows short-term safety, but what we really need is medium and long-term safety data. It is no surprise that most of the events seen were as expected in children including nasopharyngitis, upper respiratory tract infections, and nausea.”  

In the baricitinib versus placebo phase, 4.9% had serious adverse events in the baricitinib group compared to 3.7% in the placebo group. “There was nothing we didn’t expect to see which was mainly infection,” said Dr. Ramanan.

Dr. Elfayad has no disclosures. Professor Ramanan is a consultant for Eli Lilly, Abbvie, Roche, UCB, Novartis, Pfizer, and Sobi. He has received grant/research support from Eli Lilly.

COPENHAGEN – Baricitinib (Olumiant), a Janus kinase (JAK) inhibitor, significantly increases time to disease flare and decreases frequency of flares in patients with juvenile idiopathic arthritis (JIA), according to the results of a phase 3, placebo-controlled study.

The results support use of baricitinib when biologic or conventional synthetic disease-modifying antirheumatic drugs (DMARDs) fail.

 The difference in the proportion of patients who flared between baricitinib and placebo was seen as soon as 4 weeks after half of the patients switched from active drug to placebo, at 3.7% versus 23.5% respectively, reported Athimalaipet Ramanan, MD, from the University of Bristol (England) who presented the findings of the withdrawal, efficacy, and safety study at the annual European Congress of Rheumatology.

  “Our patients and parents have been waiting for alternative drugs for JIA, so JAK inhibitors have come at the right time,” he said. “These are really very encouraging findings for families, caregivers, and patients with JIA, to have an effective oral JAK inhibitor for managing these children.”

 In reporting the key findings, Dr. Ramanan added that the majority of patients (76%) achieved a JIA-ACR (American College of Rheumatology) 30 score during the 12-week open-label phase and went on to enter the double-blind withdrawal phase of the trial.

 Baricitinib 2-mg tablets are already Food and Drug Administration approved for the treatment of adults with moderately to severely active rheumatoid arthritis. This study, sponsored by the drug manufacturer Eli Lilly, aimed to investigate the efficacy and safety in pediatric patients with JIA who have shown an inadequate response to conventional synthetic or biologic DMARDs.

“For juvenile patients we need to make a dose adjustment [from the adult dosing], especially because we don’t have long-term safety data from JAK inhibitors in general,” said Osama Elfayad, MD, rheumatologist from Mouwasat Hospital, Dammam, Saudi Arabia who attended the presentation and commented on the findings.

He emphasized that safety was of primary concern in the pediatric population who have a long life expectancy. “For me it is essential to have good long-term safety data in juvenile patients. If we start with 4 mg and if the patient is controlled, we should shift to 2 mg which will be much better. I understand some clinicians are asking for 1 mg.”

Study details

The study population included patients aged from 2 to 17 years old with extended oligo- or polyarticular JIA, enthesitis-related juvenile idiopathic arthritis (ERA) and juvenile psoriatic arthritis.

 The trial was divided into three periods: a 2-week safety assessment, a 12-week open-label lead-in phase, and an up-to 32-week double-blind withdrawal phase. After confirmation of dose and safety, children were enrolled in the open-label phase receiving age-based, oral, once daily doses of baricitinib.

 “The primary endpoint is really concerned with the next phase of the study [double-blind withdrawal phase] looking at the proportion of patients who have shown a response at week 12 [achieved JIA-ACR30] but when switched from active drug to placebo have a flare,” explained Dr. Ramanan.

Patients were randomized 1:1 to continuing baricitinib or newly starting placebo until disease flare or up to week 32. The time to flare during the double-blind phase was the primary endpoint, while secondary endpoints included JIA-ACR30/50/70/90 response rates at week 12, and the proportion of patients with a flare during the double-blind phase.

 “These secondary endpoints are more relevant to the clinic,” noted Dr. Ramanan.

 A total of 219 patients entered the open-label phase, and of these, 163 achieved a JIA-ACR 30. These 163 children entered the double-blind stage and were randomized to baricitinib four times a day (56 completed), or placebo (32 completed).

 Two-thirds of patients were female, which is typical of the disease, explained Dr. Ramanan, and over two-thirds were White. “Most patients had had disease for around 4 years, and about half had had prior biologic therapy. About half were on baseline methotrexate and almost one-third had used corticosteroids although at doses of under 0.2mg/kg.

“It’s gratifying to see that over 75% achieved a JIA-ACR 30 [76.3%]. More importantly, two-thirds of the patients have a JIA-ACR 50 [63.5%], and almost half of the patients have a JIA-ACR 70 [46.1%]. This is pretty significant at 12 weeks only,” he remarked.

The key finding, however, was in the withdrawal phase, said Dr. Ramanan. “We see that those patients who had a response at week 12 and were then switched to placebo, about half [50.6%] flared on placebo, compared to only 17% of those who continued with baricitinib. So not only do those who switch to placebo have a higher frequency of flares but they are more likely to flare quickly, as early as 4 weeks.”

With respect to safety, he said: “This shows short-term safety, but what we really need is medium and long-term safety data. It is no surprise that most of the events seen were as expected in children including nasopharyngitis, upper respiratory tract infections, and nausea.”  

In the baricitinib versus placebo phase, 4.9% had serious adverse events in the baricitinib group compared to 3.7% in the placebo group. “There was nothing we didn’t expect to see which was mainly infection,” said Dr. Ramanan.

Dr. Elfayad has no disclosures. Professor Ramanan is a consultant for Eli Lilly, Abbvie, Roche, UCB, Novartis, Pfizer, and Sobi. He has received grant/research support from Eli Lilly.

A host of psoriatic arthritis symptoms can be improved by the investigational interleukin (IL)-17 blocker izokibep, according to the results of a phase 2 trial presented at the annual European Congress of Rheumatology.

Around half of all participants in the trial who were treated with izokibep achieved a 50% or higher improvement in American College of Rheumatology response criteria (ACR50) at week 16, the trial’s primary endpoint. This was highly significant (P = .0003) when compared to the control group, where only 13% of patients given a placebo achieved an ACR50.

There was also a significant improvement in skin symptoms, as assessed by the Psoriasis Area and Severity Index (PASI) and resolution of enthesitis in 88% of patients given the highest dose of izokibep.

Aurelie Najm, MD, PhD, of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, who tweeted about the main results, said that the data also looked “promising for the enthesitis domain” with a “safety profile similar to that observed in PsO [psoriasis].”Peter Taylor, MA, PhD, FRCP, FRCPE, of the University of Oxford in England, said: “The improvements demonstrated in arthritis, psoriasis, and enthesitis are exciting relative to responses reported for the current standard of care.”

He continued, in a statement issued jointly by Affibody, Acelyrin, and Immagene Biopharmaceuticals – the three companies assessing izokibep’s therapeutic potential – that the drug “seems promising” and that he was “eager to see its continued development for patients.”

Small and potent, a novel IL-17 inhibitor

Izokibep is an antibody mimetic that inhibits IL-17A designed to “overcome the limitations of monoclonal antibodies,” according to its developers.

Due to its small molecular size – reportedly about one-tenth of the size of a monoclonal antibody – they say that levels of high drug exposure can be achieved from a single, subcutaneous injection rather than an intravenous infusion, which is needed for monoclonal antibodies.

Moreover, izokibep’s small size means it could potentially reach target tissues “that may otherwise be inaccessible to the much larger monoclonal antibodies.” 

So far more than 300 patients have been treated with izokibep, some for up to 3 years, but not all have had psoriatic arthritis. Indeed, the drug has been tested in patients with psoriasis, and there are a few actively recruiting trials including one in ankylosing spondylitis, another in noninfective uveitis, and one in the rare and painful skin condition hidradenitis suppurativa.

Testing two doses of izokibep in psoriatic arthritis

The trial presented at the EULAR 2022 Congress tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active psoriatic arthritis. For inclusion in the trial patients had to have at least three swollen and at least three tender joints and have had an inadequate response to prior therapy including nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors.

Principle investigator Frank Behrens, MD, of Goethe University Frankfurt, Germany, reported that it was a multicenter effort conducted at 22 European sites with the primary endpoint being an ACR50 response at 16 weeks. This was met by 52% of patients given the 80-mg dose of izokibep, 48% of patients given the 40-mg dose of izokibep, and just 13% of patients who had been randomized to placebo.

ACR20 and ACR70 response were one of several key secondary endpoints tested, again at 16 weeks, with a respective 75%, 60%, and 20% of patients in each group achieving the lower response target and 20%, 32%, and 5%, achieving the more stringent response target.

“Izokibep demonstrated a robust efficacy in the musculoskeletal arthritic domains, but also in the extra-articular musculoskeletal domain,” Dr. Behrens said.

Not only that, but the values were “at the top end” of what’s been demonstrated for drugs currently regarded as the standard of care.

More than 80% of patients achieved a PASI75 response and 57% a PASI50 response with the two doses of izokibep, and 63%-88% achieved a resolution of enthesitis. The latter was measured using the Leeds Enthesitis Index.

There was also improvement in quality of life, measured using the Psoriatic Impact of Disease questionnaire, with a percentage increase beyond the MCID of 31%-41% with izokibep versus 12% for placebo.

“These are the first data of the phase 2 study in psoriatic arthritis,” Dr. Behrens reported.

“The safety profile was consistent with placebo,” with the only “standout aspect” being a higher number of injection-site reactions with izokibep versus placebo; but there were no serious infections, no serious adverse events,” he added.

“The interesting thing is from the preclinical research there was no dose-limiting toxicity with izokibep, therefore, I think the plan in the future is maybe to increase the dose to optimize treatment outcome based on the really robust effectiveness we see here in the first study in this clinical trial,” he said.

As a small study, stratifying results by gender wasn’t an option, Dr. Behrens noted in answering a question during the discussion period, but might be something that will be included in future and larger trials based on the post-hoc findings of other IL-17 trials.

Moving forward, the next step will involve a phase 2b/3 pivotal study which will likely include a higher dosing regimen of 160 mg once weekly alongside the twice-weekly dosing used in this trial.

Izokibep is an investigational treatment being developed by Affibody AB, Sweden, and ACELYRIN, USA. All three companies funded the phase 2 trial and were involved in the study design, conduct and reporting of results.

Dr. Behrens and Dr. Taylor were investigators in the study.

Dr. Behrens disclosed he was a shareholder of Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc. and Novartis; part of the speakers’ bureau for Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie; a consultant of AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc.; and had received grant or research support from Pfizer, Janssen, Chugai, Celgene and Roche

Dr. Taylor acknowledged grant or research support from: Celgene and Galapagos, and acted as a consultant for AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi and UCB.
 

A host of psoriatic arthritis symptoms can be improved by the investigational interleukin (IL)-17 blocker izokibep, according to the results of a phase 2 trial presented at the annual European Congress of Rheumatology.

Around half of all participants in the trial who were treated with izokibep achieved a 50% or higher improvement in American College of Rheumatology response criteria (ACR50) at week 16, the trial’s primary endpoint. This was highly significant (P = .0003) when compared to the control group, where only 13% of patients given a placebo achieved an ACR50.

There was also a significant improvement in skin symptoms, as assessed by the Psoriasis Area and Severity Index (PASI) and resolution of enthesitis in 88% of patients given the highest dose of izokibep.

Aurelie Najm, MD, PhD, of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, who tweeted about the main results, said that the data also looked “promising for the enthesitis domain” with a “safety profile similar to that observed in PsO [psoriasis].”Peter Taylor, MA, PhD, FRCP, FRCPE, of the University of Oxford in England, said: “The improvements demonstrated in arthritis, psoriasis, and enthesitis are exciting relative to responses reported for the current standard of care.”

He continued, in a statement issued jointly by Affibody, Acelyrin, and Immagene Biopharmaceuticals – the three companies assessing izokibep’s therapeutic potential – that the drug “seems promising” and that he was “eager to see its continued development for patients.”

Small and potent, a novel IL-17 inhibitor

Izokibep is an antibody mimetic that inhibits IL-17A designed to “overcome the limitations of monoclonal antibodies,” according to its developers.

Due to its small molecular size – reportedly about one-tenth of the size of a monoclonal antibody – they say that levels of high drug exposure can be achieved from a single, subcutaneous injection rather than an intravenous infusion, which is needed for monoclonal antibodies.

Moreover, izokibep’s small size means it could potentially reach target tissues “that may otherwise be inaccessible to the much larger monoclonal antibodies.” 

So far more than 300 patients have been treated with izokibep, some for up to 3 years, but not all have had psoriatic arthritis. Indeed, the drug has been tested in patients with psoriasis, and there are a few actively recruiting trials including one in ankylosing spondylitis, another in noninfective uveitis, and one in the rare and painful skin condition hidradenitis suppurativa.

Testing two doses of izokibep in psoriatic arthritis

The trial presented at the EULAR 2022 Congress tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active psoriatic arthritis. For inclusion in the trial patients had to have at least three swollen and at least three tender joints and have had an inadequate response to prior therapy including nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors.

Principle investigator Frank Behrens, MD, of Goethe University Frankfurt, Germany, reported that it was a multicenter effort conducted at 22 European sites with the primary endpoint being an ACR50 response at 16 weeks. This was met by 52% of patients given the 80-mg dose of izokibep, 48% of patients given the 40-mg dose of izokibep, and just 13% of patients who had been randomized to placebo.

ACR20 and ACR70 response were one of several key secondary endpoints tested, again at 16 weeks, with a respective 75%, 60%, and 20% of patients in each group achieving the lower response target and 20%, 32%, and 5%, achieving the more stringent response target.

“Izokibep demonstrated a robust efficacy in the musculoskeletal arthritic domains, but also in the extra-articular musculoskeletal domain,” Dr. Behrens said.

Not only that, but the values were “at the top end” of what’s been demonstrated for drugs currently regarded as the standard of care.

More than 80% of patients achieved a PASI75 response and 57% a PASI50 response with the two doses of izokibep, and 63%-88% achieved a resolution of enthesitis. The latter was measured using the Leeds Enthesitis Index.

There was also improvement in quality of life, measured using the Psoriatic Impact of Disease questionnaire, with a percentage increase beyond the MCID of 31%-41% with izokibep versus 12% for placebo.

“These are the first data of the phase 2 study in psoriatic arthritis,” Dr. Behrens reported.

“The safety profile was consistent with placebo,” with the only “standout aspect” being a higher number of injection-site reactions with izokibep versus placebo; but there were no serious infections, no serious adverse events,” he added.

“The interesting thing is from the preclinical research there was no dose-limiting toxicity with izokibep, therefore, I think the plan in the future is maybe to increase the dose to optimize treatment outcome based on the really robust effectiveness we see here in the first study in this clinical trial,” he said.

As a small study, stratifying results by gender wasn’t an option, Dr. Behrens noted in answering a question during the discussion period, but might be something that will be included in future and larger trials based on the post-hoc findings of other IL-17 trials.

Moving forward, the next step will involve a phase 2b/3 pivotal study which will likely include a higher dosing regimen of 160 mg once weekly alongside the twice-weekly dosing used in this trial.

Izokibep is an investigational treatment being developed by Affibody AB, Sweden, and ACELYRIN, USA. All three companies funded the phase 2 trial and were involved in the study design, conduct and reporting of results.

Dr. Behrens and Dr. Taylor were investigators in the study.

Dr. Behrens disclosed he was a shareholder of Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc. and Novartis; part of the speakers’ bureau for Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie; a consultant of AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc.; and had received grant or research support from Pfizer, Janssen, Chugai, Celgene and Roche

Dr. Taylor acknowledged grant or research support from: Celgene and Galapagos, and acted as a consultant for AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi and UCB.
 

A host of psoriatic arthritis symptoms can be improved by the investigational interleukin (IL)-17 blocker izokibep, according to the results of a phase 2 trial presented at the annual European Congress of Rheumatology.

Around half of all participants in the trial who were treated with izokibep achieved a 50% or higher improvement in American College of Rheumatology response criteria (ACR50) at week 16, the trial’s primary endpoint. This was highly significant (P = .0003) when compared to the control group, where only 13% of patients given a placebo achieved an ACR50.

There was also a significant improvement in skin symptoms, as assessed by the Psoriasis Area and Severity Index (PASI) and resolution of enthesitis in 88% of patients given the highest dose of izokibep.

Aurelie Najm, MD, PhD, of the Institute of Infection, Immunity and Inflammation at the University of Glasgow, who tweeted about the main results, said that the data also looked “promising for the enthesitis domain” with a “safety profile similar to that observed in PsO [psoriasis].”Peter Taylor, MA, PhD, FRCP, FRCPE, of the University of Oxford in England, said: “The improvements demonstrated in arthritis, psoriasis, and enthesitis are exciting relative to responses reported for the current standard of care.”

He continued, in a statement issued jointly by Affibody, Acelyrin, and Immagene Biopharmaceuticals – the three companies assessing izokibep’s therapeutic potential – that the drug “seems promising” and that he was “eager to see its continued development for patients.”

Small and potent, a novel IL-17 inhibitor

Izokibep is an antibody mimetic that inhibits IL-17A designed to “overcome the limitations of monoclonal antibodies,” according to its developers.

Due to its small molecular size – reportedly about one-tenth of the size of a monoclonal antibody – they say that levels of high drug exposure can be achieved from a single, subcutaneous injection rather than an intravenous infusion, which is needed for monoclonal antibodies.

Moreover, izokibep’s small size means it could potentially reach target tissues “that may otherwise be inaccessible to the much larger monoclonal antibodies.” 

So far more than 300 patients have been treated with izokibep, some for up to 3 years, but not all have had psoriatic arthritis. Indeed, the drug has been tested in patients with psoriasis, and there are a few actively recruiting trials including one in ankylosing spondylitis, another in noninfective uveitis, and one in the rare and painful skin condition hidradenitis suppurativa.

Testing two doses of izokibep in psoriatic arthritis

The trial presented at the EULAR 2022 Congress tested two doses of izokibep – 40 mg and 80 mg – given by subcutaneous injection every 2 weeks – against placebo in 135 adult patients with active psoriatic arthritis. For inclusion in the trial patients had to have at least three swollen and at least three tender joints and have had an inadequate response to prior therapy including nonsteroidal anti-inflammatory drugs, conventional synthetic disease-modifying antirheumatic drugs, or tumor necrosis factor inhibitors.

Principle investigator Frank Behrens, MD, of Goethe University Frankfurt, Germany, reported that it was a multicenter effort conducted at 22 European sites with the primary endpoint being an ACR50 response at 16 weeks. This was met by 52% of patients given the 80-mg dose of izokibep, 48% of patients given the 40-mg dose of izokibep, and just 13% of patients who had been randomized to placebo.

ACR20 and ACR70 response were one of several key secondary endpoints tested, again at 16 weeks, with a respective 75%, 60%, and 20% of patients in each group achieving the lower response target and 20%, 32%, and 5%, achieving the more stringent response target.

“Izokibep demonstrated a robust efficacy in the musculoskeletal arthritic domains, but also in the extra-articular musculoskeletal domain,” Dr. Behrens said.

Not only that, but the values were “at the top end” of what’s been demonstrated for drugs currently regarded as the standard of care.

More than 80% of patients achieved a PASI75 response and 57% a PASI50 response with the two doses of izokibep, and 63%-88% achieved a resolution of enthesitis. The latter was measured using the Leeds Enthesitis Index.

There was also improvement in quality of life, measured using the Psoriatic Impact of Disease questionnaire, with a percentage increase beyond the MCID of 31%-41% with izokibep versus 12% for placebo.

“These are the first data of the phase 2 study in psoriatic arthritis,” Dr. Behrens reported.

“The safety profile was consistent with placebo,” with the only “standout aspect” being a higher number of injection-site reactions with izokibep versus placebo; but there were no serious infections, no serious adverse events,” he added.

“The interesting thing is from the preclinical research there was no dose-limiting toxicity with izokibep, therefore, I think the plan in the future is maybe to increase the dose to optimize treatment outcome based on the really robust effectiveness we see here in the first study in this clinical trial,” he said.

As a small study, stratifying results by gender wasn’t an option, Dr. Behrens noted in answering a question during the discussion period, but might be something that will be included in future and larger trials based on the post-hoc findings of other IL-17 trials.

Moving forward, the next step will involve a phase 2b/3 pivotal study which will likely include a higher dosing regimen of 160 mg once weekly alongside the twice-weekly dosing used in this trial.

Izokibep is an investigational treatment being developed by Affibody AB, Sweden, and ACELYRIN, USA. All three companies funded the phase 2 trial and were involved in the study design, conduct and reporting of results.

Dr. Behrens and Dr. Taylor were investigators in the study.

Dr. Behrens disclosed he was a shareholder of Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc. and Novartis; part of the speakers’ bureau for Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion and AbbVie; a consultant of AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc.; and had received grant or research support from Pfizer, Janssen, Chugai, Celgene and Roche

Dr. Taylor acknowledged grant or research support from: Celgene and Galapagos, and acted as a consultant for AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi and UCB.
 

An investigational agent has shown promise in a subgroup of patients with advanced pancreatic cancer, offering hope of a clinical advance in a cancer that remains very difficult to treat. 

The drug is nimotuzumab, developed as a joint Chinese-Cuban venture, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), inhibiting tumor cells that overexpress EGFR.

When nimotuzumab was added to gemcitabine, it significantly improved overall survival, compared with gemcitabine alone, in a trial conducted in China in 92 patients with advanced pancreatic cancer who had KRAS wild-type tumors.

One-year survival rates were 43.6% with nimotuzumab versus 26.8% with placebo, while 3-year survival rates were 13.9% versus 2.7%.

The results were presented at the annual meeting of the American Society of Clinical Oncology and highlighted at a press briefing.

“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer,” co-lead author Shukui Qin, MD, department of medical oncology, Cancer Center, Jinling Hospital, Nanjing, China, commented in an ASCO press release.

“The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer,” he added. 

“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest,” commented Cathy Eng, MD, an ASCO expert in gastrointestinal cancers.

However, she pointed out that the subgroup of patients who may benefit is small – KRAS wild-type tumors are found in fewer than 10% of patients with pancreatic cancer.

“Additional studies in comparison with the combination of gemcitabine/nab-paclitaxel would be of interest,” Dr. Eng added, to validate “any potential advances to make a true difference in the lives of all patients with pancreatic cancer.”
 

Already marketed in China

Nimotuzumab is already marketed in China: It was approved in 2008 by the Chinese National Medical Products Administration for the treatment of nasopharyngeal carcinoma and is currently being investigated in head and neck, cervical, esophageal, and other cancers.

Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, commented in an interview that it will be “interesting to see the U.S. Food and Drug Administration’s response to the current data.”

She explained that the FDA has recently rejected drugs developed and tested in China, mostly notably sintilimab in non–small cell lung cancer, because the clinical data submitted were from China and not “reflective of the U.S. cancer population” and also because in this case there were already a number of other similar drugs available in this therapeutic area.

However, pancreatic cancer represents an unmet clinical need, which is a different situation, and there may be some consideration for an accelerated approval while awaiting a U.S. clinical trial, she speculated.

This trial showed an interesting proof of principle, she added – it showed that an EGRF inhibitor was active in KRAS wild-type advanced pancreatic cancer. This opens the door for exploration with other drugs that also act as EGFR blockers, as well as drugs with other actions such as BRAF antagonists, MAP kinase inhibitors, and/or immunotherapy.  
 

Study details

The phase 3 NOTABLE trial involved 92 Chinese patients with locally advanced or metastatic KRAS wild-type pancreatic cancer randomized to nimotuzumab weekly or placebo plus gemcitabine until progression or unacceptable toxicity.

Median overall survival was significantly longer with nimotuzumab, at 10.9 versus 8.5 months with placebo, at a hazard ratio of 0.50.

The results showed that median progression-free survival (PFS) was also significantly longer among patients given nimotuzumab, at 4.2 versus 3.6 months in the placebo group, or a hazard ratio of 0.56.

Patients were then stratified based on whether they needed surgery to remove bile duct obstructions prior to chemotherapy, as those not requiring surgery tend to have better liver function and so may better tolerate chemotherapy.

The overall survival benefit with nimotuzumab was greater among patients with no surgical history, at 15.8 versus 6.0 months with placebo, at a hazard ratio of 0.40, compared with 11.9 versus 8.5 months among those with biliary obstruction, at a hazard ratio of 0.54.

Patients who did not receive treatment for biliary obstruction had a significantly longer PFS than those who underwent surgery, at 5.5 versus 3.4 months (P = .008).

The researchers report that the incidence of adverse events in the nimotuzumab group was similar to that among patients given placebo.

The most common grade 3 treatment-related adverse events with the combination therapy were neutropenia, in 11.1% of patients, leukopenia (8.9%), and thrombocytopenia (6.7%). There were no grade 4 adverse events.

The study was sponsored by Biotech Pharmaceutical. Dr. Qin has disclosed no relevant financial relationships. Dr. Eng has disclosed relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer. Dr. Gralow has disclosed relationships with Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, and Genomic Health.

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

An investigational agent has shown promise in a subgroup of patients with advanced pancreatic cancer, offering hope of a clinical advance in a cancer that remains very difficult to treat. 

The drug is nimotuzumab, developed as a joint Chinese-Cuban venture, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), inhibiting tumor cells that overexpress EGFR.

When nimotuzumab was added to gemcitabine, it significantly improved overall survival, compared with gemcitabine alone, in a trial conducted in China in 92 patients with advanced pancreatic cancer who had KRAS wild-type tumors.

One-year survival rates were 43.6% with nimotuzumab versus 26.8% with placebo, while 3-year survival rates were 13.9% versus 2.7%.

The results were presented at the annual meeting of the American Society of Clinical Oncology and highlighted at a press briefing.

“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer,” co-lead author Shukui Qin, MD, department of medical oncology, Cancer Center, Jinling Hospital, Nanjing, China, commented in an ASCO press release.

“The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer,” he added. 

“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest,” commented Cathy Eng, MD, an ASCO expert in gastrointestinal cancers.

However, she pointed out that the subgroup of patients who may benefit is small – KRAS wild-type tumors are found in fewer than 10% of patients with pancreatic cancer.

“Additional studies in comparison with the combination of gemcitabine/nab-paclitaxel would be of interest,” Dr. Eng added, to validate “any potential advances to make a true difference in the lives of all patients with pancreatic cancer.”
 

Already marketed in China

Nimotuzumab is already marketed in China: It was approved in 2008 by the Chinese National Medical Products Administration for the treatment of nasopharyngeal carcinoma and is currently being investigated in head and neck, cervical, esophageal, and other cancers.

Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, commented in an interview that it will be “interesting to see the U.S. Food and Drug Administration’s response to the current data.”

She explained that the FDA has recently rejected drugs developed and tested in China, mostly notably sintilimab in non–small cell lung cancer, because the clinical data submitted were from China and not “reflective of the U.S. cancer population” and also because in this case there were already a number of other similar drugs available in this therapeutic area.

However, pancreatic cancer represents an unmet clinical need, which is a different situation, and there may be some consideration for an accelerated approval while awaiting a U.S. clinical trial, she speculated.

This trial showed an interesting proof of principle, she added – it showed that an EGRF inhibitor was active in KRAS wild-type advanced pancreatic cancer. This opens the door for exploration with other drugs that also act as EGFR blockers, as well as drugs with other actions such as BRAF antagonists, MAP kinase inhibitors, and/or immunotherapy.  
 

Study details

The phase 3 NOTABLE trial involved 92 Chinese patients with locally advanced or metastatic KRAS wild-type pancreatic cancer randomized to nimotuzumab weekly or placebo plus gemcitabine until progression or unacceptable toxicity.

Median overall survival was significantly longer with nimotuzumab, at 10.9 versus 8.5 months with placebo, at a hazard ratio of 0.50.

The results showed that median progression-free survival (PFS) was also significantly longer among patients given nimotuzumab, at 4.2 versus 3.6 months in the placebo group, or a hazard ratio of 0.56.

Patients were then stratified based on whether they needed surgery to remove bile duct obstructions prior to chemotherapy, as those not requiring surgery tend to have better liver function and so may better tolerate chemotherapy.

The overall survival benefit with nimotuzumab was greater among patients with no surgical history, at 15.8 versus 6.0 months with placebo, at a hazard ratio of 0.40, compared with 11.9 versus 8.5 months among those with biliary obstruction, at a hazard ratio of 0.54.

Patients who did not receive treatment for biliary obstruction had a significantly longer PFS than those who underwent surgery, at 5.5 versus 3.4 months (P = .008).

The researchers report that the incidence of adverse events in the nimotuzumab group was similar to that among patients given placebo.

The most common grade 3 treatment-related adverse events with the combination therapy were neutropenia, in 11.1% of patients, leukopenia (8.9%), and thrombocytopenia (6.7%). There were no grade 4 adverse events.

The study was sponsored by Biotech Pharmaceutical. Dr. Qin has disclosed no relevant financial relationships. Dr. Eng has disclosed relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer. Dr. Gralow has disclosed relationships with Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, and Genomic Health.

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

An investigational agent has shown promise in a subgroup of patients with advanced pancreatic cancer, offering hope of a clinical advance in a cancer that remains very difficult to treat. 

The drug is nimotuzumab, developed as a joint Chinese-Cuban venture, a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), inhibiting tumor cells that overexpress EGFR.

When nimotuzumab was added to gemcitabine, it significantly improved overall survival, compared with gemcitabine alone, in a trial conducted in China in 92 patients with advanced pancreatic cancer who had KRAS wild-type tumors.

One-year survival rates were 43.6% with nimotuzumab versus 26.8% with placebo, while 3-year survival rates were 13.9% versus 2.7%.

The results were presented at the annual meeting of the American Society of Clinical Oncology and highlighted at a press briefing.

“We believe our NOTABLE trial will be a breakthrough in the field of pancreatic cancer,” co-lead author Shukui Qin, MD, department of medical oncology, Cancer Center, Jinling Hospital, Nanjing, China, commented in an ASCO press release.

“The outcomes in this trial may bring new hope to patients with KRAS wild-type pancreatic cancer,” he added. 

“To see any survival benefit in a trial for metastatic pancreatic cancer is of interest,” commented Cathy Eng, MD, an ASCO expert in gastrointestinal cancers.

However, she pointed out that the subgroup of patients who may benefit is small – KRAS wild-type tumors are found in fewer than 10% of patients with pancreatic cancer.

“Additional studies in comparison with the combination of gemcitabine/nab-paclitaxel would be of interest,” Dr. Eng added, to validate “any potential advances to make a true difference in the lives of all patients with pancreatic cancer.”
 

Already marketed in China

Nimotuzumab is already marketed in China: It was approved in 2008 by the Chinese National Medical Products Administration for the treatment of nasopharyngeal carcinoma and is currently being investigated in head and neck, cervical, esophageal, and other cancers.

Julie R. Gralow, MD, ASCO chief medical officer and executive vice president, commented in an interview that it will be “interesting to see the U.S. Food and Drug Administration’s response to the current data.”

She explained that the FDA has recently rejected drugs developed and tested in China, mostly notably sintilimab in non–small cell lung cancer, because the clinical data submitted were from China and not “reflective of the U.S. cancer population” and also because in this case there were already a number of other similar drugs available in this therapeutic area.

However, pancreatic cancer represents an unmet clinical need, which is a different situation, and there may be some consideration for an accelerated approval while awaiting a U.S. clinical trial, she speculated.

This trial showed an interesting proof of principle, she added – it showed that an EGRF inhibitor was active in KRAS wild-type advanced pancreatic cancer. This opens the door for exploration with other drugs that also act as EGFR blockers, as well as drugs with other actions such as BRAF antagonists, MAP kinase inhibitors, and/or immunotherapy.  
 

Study details

The phase 3 NOTABLE trial involved 92 Chinese patients with locally advanced or metastatic KRAS wild-type pancreatic cancer randomized to nimotuzumab weekly or placebo plus gemcitabine until progression or unacceptable toxicity.

Median overall survival was significantly longer with nimotuzumab, at 10.9 versus 8.5 months with placebo, at a hazard ratio of 0.50.

The results showed that median progression-free survival (PFS) was also significantly longer among patients given nimotuzumab, at 4.2 versus 3.6 months in the placebo group, or a hazard ratio of 0.56.

Patients were then stratified based on whether they needed surgery to remove bile duct obstructions prior to chemotherapy, as those not requiring surgery tend to have better liver function and so may better tolerate chemotherapy.

The overall survival benefit with nimotuzumab was greater among patients with no surgical history, at 15.8 versus 6.0 months with placebo, at a hazard ratio of 0.40, compared with 11.9 versus 8.5 months among those with biliary obstruction, at a hazard ratio of 0.54.

Patients who did not receive treatment for biliary obstruction had a significantly longer PFS than those who underwent surgery, at 5.5 versus 3.4 months (P = .008).

The researchers report that the incidence of adverse events in the nimotuzumab group was similar to that among patients given placebo.

The most common grade 3 treatment-related adverse events with the combination therapy were neutropenia, in 11.1% of patients, leukopenia (8.9%), and thrombocytopenia (6.7%). There were no grade 4 adverse events.

The study was sponsored by Biotech Pharmaceutical. Dr. Qin has disclosed no relevant financial relationships. Dr. Eng has disclosed relationships with Bayer Health, Gilead/Forty Seven, GlaxoSmithKline, Hookipa Biotech, Mirati Therapeutics, Natera, Pfizer, Elevar, Fruquitinib, Merck, and Pfizer. Dr. Gralow has disclosed relationships with Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, and Genomic Health.

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

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

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

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

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

Adagrasib, an investigational drug that acts as a KRASG12C inhibitor, has shown durable clinical benefit in patients with previously treated, advanced non-small cell lung cancer (NSCLC) with tumors with KRAS G12C mutations.

“KRAS G12C mutations occur in over 10% of patients with NSCL [and] remain difficult to target, and outcomes for this patient population have remained poor,” co-investigator Joshua Sabari, MD, assistant professor of medicine, Perlmutter Cancer Center at NYU Langone, said in a statement.

“Our patients benefited clinically from this agent, and it appears to have improved overall survival (OS), compared with historical outcomes with docetaxel, a standard-of-care chemotherapy regimen, in the second-line setting,” he added.

New data on adagrasib were presented at the annual meeting of the American Society for Clinical Oncology and simultaneously published in the New England Journal of Medicine.

Adagrasib (developed by Mirati) is currently awaiting approval from the U.S. Food and Drug Administration as a treatment for patients with NSCLC harboring the KRAS G12C mutation who have received at least one prior systemic therapy. This would be an accelerated approval based on overall response data from the KRYSTAL-1 study detailed below. The company has an ongoing confirmatory Phase 3 trial, KRYSTAL-12, evaluating adagrasib versus docetaxel in patients previously treated for metastatic NSCLC with a KRAS G12C mutation.

If approved, adagrasib would be the second in this class of agents. The first KRASG12C inhibitor for use in lung cancer was sotorasib (Lumakras), approved by the U.S. Food and Drug Administration in May 2021.  

Dr. Sabari noted that there are several differences between the two drugs. Adagrasib has CNS penetration and is the first KRASG12C inhibitor to demonstrate clinical activity in patients with KRAS G12C-mutated NSCLC with untreated active CNS metastases.
 

Published clinical data

The results published in the New England Journal of Medicine are from the company-funded KRYSTAL-1 clinical trial, which had the primary endpoint of objective response rate.

It was conducted in patients with KRAS G12C-mutated NSCLC who had previously received treatment with at least one platinum-containing chemotherapy regimen and checkpoint inhibitor therapy either sequentially or concurrently.

Patients were treated with oral adagrasib 600 mg twice a day until disease progression, unacceptable toxicity, or death.

On Oct. 15, 2021, the data cutoff date, a total of 116 patients had received at least one dose of adagrasib. At a median follow-up of 12.9 months, the confirmed objective response rate was 42.9% among 112 patients with measurable disease at baseline. One patient achieved a complete response: 42% achieved a partial response, and disease stabilized for a minimum of 6 weeks in over 36% of the group.

Only 5.4% of patients had progressive disease as their best overall response, investigators note. Among those patients who responded to twice-daily KRASG12C inhibition, the median time to response was 1.4 months and the median duration of response was 8.5 months. As of the data cutoff date, one-third of the group were still receiving treatment, the authors note.

Median progression-free survival (PFS) was 6.5 months and median OS was 11.7 months. With a longer median follow-up of 15.6 months, median OS was 12.6 months, and the estimated OS at 1 year was close to 51%.

“The majority of treatment-related adverse events were low-grade, started early in treatment, and quickly resolved after occurrence,” Dr. Sabari noted.

Grade 1-2 treatment-related adverse events occurred in 53% of patients while 45% had grade 3-4 treatment-related adverse events, and there were two fatal grade 5 treatment-related adverse events. The same events led to a dose reduction in 52% of the group overall and dose interruption in 61%, while in 7% of patients, treatment-related adverse events led to discontinuation of the drug.
 

CNS metastases

At baseline, some 42 patients had evidence of central nervous system (CNS) metastases. At a median follow-up of 15.4 months, an intracranial-confirmed objective response was achieved in one-third of this subgroup overall while median duration of the intracranial response was 11.2 months. Again, within the same subgroup, the median PFS was 5.4 months.

As Dr. Sabari noted, CNS metastases from KRAS mutant NSCLC are common. “Adagrasib demonstrated encouraging and durable CNS-specific activity in patients with KRAS G12C-mutant NSCLC and active, untreated CNS metastases,” he said.

The study was funded by Mirati Therapeutics.

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

CHICAGO -- A “liquid biopsy” that detects circulating tumor DNA (ctDNA) after surgery for stage 2 colon cancer helps identify patients most likely to benefit from adjuvant chemotherapy and also identifies those who are unlikely to benefit, allowing them to skip that treatment.

The results are from the phase 2 DYNAMIC trial.

“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.

The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.

The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.

Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.

The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.

The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.

“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.

“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.

They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
 

Study details

For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.

The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.

Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).

Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.

ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”

Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
 

Next steps

The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.

The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.  

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

CHICAGO -- A “liquid biopsy” that detects circulating tumor DNA (ctDNA) after surgery for stage 2 colon cancer helps identify patients most likely to benefit from adjuvant chemotherapy and also identifies those who are unlikely to benefit, allowing them to skip that treatment.

The results are from the phase 2 DYNAMIC trial.

“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.

The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.

The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.

Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.

The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.

The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.

“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.

“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.

They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
 

Study details

For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.

The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.

Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).

Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.

ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”

Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
 

Next steps

The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.

The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.  

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

CHICAGO -- A “liquid biopsy” that detects circulating tumor DNA (ctDNA) after surgery for stage 2 colon cancer helps identify patients most likely to benefit from adjuvant chemotherapy and also identifies those who are unlikely to benefit, allowing them to skip that treatment.

The results are from the phase 2 DYNAMIC trial.

“The strategy of using ctDNA results to inform treatment almost halved the number of patients who received chemotherapy postsurgery, from 28% down to 15%,” commented first author Jeanne Tie, MD, from the Walter and Eliza Hall Institute of Medical Research at the Peter MacCallum Cancer Centre, University of Melbourne.

The overall proportion of patients who were alive and cancer-free at 3 years after ctDNA-guided treatment was 92% – the same as in patients randomized to standard management, she added.

The chance of being alive and cancer-free was 86.4% and 92.5%, respectively, in ctDNA-positive patients who received adjuvant chemotherapy and in ctDNA-negative patients who did not, she said. Conversely, the risk of recurrence is greater than 80% without treatment in ctDNA-positive patients, said Dr. Tie.

Dr. Tie reported the results at the annual meeting of the American Society of Clinical Oncology, which were simultaneously published in the New England Journal of Medicine.

The study supports a ctDNA-guided approach to treatment in this patient population, Dr. Tie said, noting that this approach addresses what has been a clinical dilemma: Surgery can cure more than 80% of stage 2 patients, but the benefits of chemotherapy after surgery have been less clear – fewer than 1 in 20 patients will benefit, but the ability to predict which patients will benefit has been lacking.

The findings are practice-changing, commented Julie Gralow, MD, ASCO’s chief medical officer and executive vice president.

“I see this study as an important kind of new concept in cancers, where for the most part we have really very good survival and outcomes ... and now we’re starting to look at ways we can deescalate therapy in a subgroup who we know are going to do well while continuing the more intensive therapy, or even escalating therapy, in the group who we know are not going to do well with our conventional therapies,” Dr. Gralow said at a press briefing where the study was highlighted.

“I do believe the results are going to help us guide our selection of who benefits from chemo and who can avoid it – and all the toxicities of it – in stage 2 colon cancer,” she added.

They may also identify patients who may need more than standard treatment. This is a group in which “we might need to think outside the box and do even more besides just thinking about adjuvant chemo,” she told this news organization in a preconference interview. “Maybe this is a group we should be thinking about adjuvant immunotherapy, for example, or adjuvant EGFR-targeted therapy, or other things that we have shown [to have benefit] in the metastatic setting.”
 

Study details

For the DYNAMIC trial, Dr. Tie and colleagues enrolled 455 patients with resected stage 2 colon cancer at multiple centers between August 2015 and August 2019. Of those, 302 were randomized to receive ctDNA-guided chemotherapy and 153 received standard management based on conventional criteria, including tumor stage of disease, number of lymph nodes assessed, whether the tumor had perforated the bowel wall, and other factors.

The Safe-SeqS tumor-informed personalized ctDNA assay was used to detect ctDNA in the experimental group. Patients with a ctDNA-positive result at 4 or 7 weeks after surgery received oxaliplatin-based or fluoropyrimidine chemotherapy; those who were ctDNA-negative were observed during follow-up.

Fewer patients overall in the ctDNA-guided group, compared with the standard management group, received adjuvant chemotherapy (15.3% vs. 27.9%; odds ratio, 2.14).

Two-year recurrence-free survival (RFS) in the ctDNA-guided treatment group was noninferior to that in the standard management group (93.5% vs. 92.4%). Three-year RFS was 86.4% in ctDNA-positive patients who received chemotherapy, 92.5% in ctDNA-negative patients without chemotherapy, and 96.7% in a clinical low-risk subgroup.

ASCO expert Cathy Eng, MD, applauded the findings, stating in a press release that “thanks to the results of this study, we may now be able to use it to better identify which patient with stage 2 colon cancer would benefit from post surgery treatment with chemotherapy and which ones can be spared the additional treatment, without compromising relapse-free survival.”

Dr. Eng is the David H. Johnson Chair in Surgical and Medical Oncology, co-leader of the Gastrointestinal Cancer Research Program, co-director of GI oncology, and professor of medicine in hematology and oncology at Vanderbilt University, Nashville, Tenn.
 

Next steps

The authors note that a randomized trial is being considered in which ctDNA-positive and -negative patients would be randomized to treatment versus no treatment. This could provide more definitive evidence of treatment impact, or lack of impact, in each of the patient subsets, according to the press release.

The DYNAMIC trial was funded by the Australian National Health and Medical Research Council, U.S. National Institutes of Health, the Marcus Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Lustgarten Foundation, the Conrad R. Hilton Foundation, the Sol Goldman Charitable Trust, John Templeton Foundation, and Eastern Health Research Foundation. Dr. Tie has reported receiving honoraria from Inivata and Servier and serving as a consultant or advisor for AstraZeneca/MedImmune, Bristol-Myers Squibb, Haystack Oncology, Inivata, MSD Oncology, and Pierre Fabre.  

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