Lung Cancer

There was no evidence of an abscopal effect with the addition of limited radiation therapy to nivolumab in patients with metastatic head and neck squamous cell carcinoma, according to new results from a randomized trial. 

The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.

The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.

The finding indicates that there was no abscopal effect, the team concluded.

The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.

This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.

In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.

“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.

Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.

A more emphatic statement comes from a pair of oncologists in an accompanying editorial.

The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.

This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.

The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.

It’s time to put the abscopal effect to rest, suggested Dr. Lee.

“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.

The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”

Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.

On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
 

Radiation and immunotherapy combinations

Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.

There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.

They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.

Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.

The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”

The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.

Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.

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

There was no evidence of an abscopal effect with the addition of limited radiation therapy to nivolumab in patients with metastatic head and neck squamous cell carcinoma, according to new results from a randomized trial. 

The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.

The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.

The finding indicates that there was no abscopal effect, the team concluded.

The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.

This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.

In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.

“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.

Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.

A more emphatic statement comes from a pair of oncologists in an accompanying editorial.

The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.

This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.

The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.

It’s time to put the abscopal effect to rest, suggested Dr. Lee.

“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.

The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”

Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.

On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
 

Radiation and immunotherapy combinations

Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.

There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.

They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.

Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.

The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”

The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.

Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.

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

There was no evidence of an abscopal effect with the addition of limited radiation therapy to nivolumab in patients with metastatic head and neck squamous cell carcinoma, according to new results from a randomized trial. 

The phase 2, single-center study was conducted in 62 patients with head and neck cancer and at least two metastatic lesions. They were randomly assigned to receive nivolumab with or without additional radiation, delivered as stereotactic body radiation therapy (SBRT), but directed at only one of the metastatic lesions.

The results showed a similar rate of tumor shrinkage and disappearance in both groups (34.5% for nivolumab vs. 29.0% for the combination; P = .86) reported Sean McBride, MD, MPH, Memorial Sloan Kettering Cancer Center, New York, and colleagues in a paper published online in the Journal of Clinical Oncology.

The finding indicates that there was no abscopal effect, the team concluded.

The abscopal (from the Latin ab “away from” and scopus “target”) effect, first described in the 1950s, is a hypothetical result of radiation, whereby tumors situated outside the radiation field are reduced or eliminated by an assumed reaction mediated by the immune system.

This study is only the second randomized controlled trial to look at this effect. A previous trial in lung cancer (JAMA Oncol. 2019;5:1276) also failed to show a significant difference in objective response rate, the primary outcome.

In both studies, there was also no improvement in progression-free survival (PFS) or overall survival (OS) with the addition of radiation.

“There are still die-hard proponents of the existence of an abscopal response, but it is clear from our data – there is no abscopal response,” lead study author Nancy Lee, MD, said in an interview.

Dr. Lee, also from Memorial Sloan Kettering, was referring to this trial in head and neck cancer specifically. But previous nonrandomized studies have also reported response rates for the combination of SBRT and immunotherapy that are similar to monotherapy, the authors point out. Overall, the collective data in oncology suggest that the abscopal response is “relatively rare,” the team comments.

A more emphatic statement comes from a pair of oncologists in an accompanying editorial.

The new study “provides the clearest evidence so far that the abscopal effect, contrary to widely held perception in the field, remains exceedingly rare,” wrote Tanguy Seiwert, MD, medical oncologist, and Ana Kiess, MD, PhD, radiation oncologist, both at Johns Hopkins University, Baltimore.

This is a “well-executed study that has broader implications beyond head and neck cancer and speaks to larger issues of combination therapies in the era of cancer immunotherapy,” they also wrote.

The practice of using limited SBRT on any tumor type – along with anti–PD-1/PD-L1 therapy – “should not be pursued for the sole purpose of induction of an abscopal effect until we have better data to support any benefit,” the editorialists added.

It’s time to put the abscopal effect to rest, suggested Dr. Lee.

“Instead of focusing on whether an abscopal response exists or not, as it clearly did not in our phase 2 study, our focus should shift to the broader picture. What is the optimal timing of PD-1 or PD-L1 therapy in relation to radiotherapy?” she said.

The answer appears to be sequentially – and not concurrently, which is how radiation has been used to induce the would-be abscopal effect, she explained. “I personally feel that immunotherapy should not be given concurrently with radiation therapy.”

Damning data for the concurrent approach come from the phase 3 Javelin Head and Neck 100 trial, she said. In March, trial sponsors announced that the trial was terminated as it was unlikely to meet its primary endpoint. Specifically, adding an anti–PD-L1 therapy to chemoradiotherapy was not superior to chemoradiotherapy alone.

On the other hand, in the phase 3 lung cancer study known as PACIFIC, chemoradiotherapy followed by sequential anti–PD-L1 therapy showed “dramatic” improvements in PFS and OS, the editorialists pointed out.
 

Radiation and immunotherapy combinations

Despite the failure of this trial, radiation has “significant potential for combination with immunotherapy,” observed Dr. Seiwert and Dr. Kiess.

There are at least three potential roles of radiation therapy in combination with anti–PD-1/PD-L1 therapy, they wrote.

They explained that the first is single-site palliative radiation therapy/SBRT, which can control local symptoms. The second is “consolidation” of all tumor sites with radiation therapy/SBRT, which may decrease tumor burden and heterogeneity. And the third potential role is definitive locoregional radiation therapy to achieve long-term locoregional tumor control.

Thus, the editorialists, like Dr. Lee, believed the question of concurrent versus sequential immunotherapy is “important.” But the field of oncology has an abundance of treatments that can now be aimed at a cancer, in a variety of potential combinations, they observed.

The editorialists concluded their commentary with a long list of needed work: “We should take this study to guide us to explore promising approaches in rigorous clinical trials, with a focus on sequential approaches such as definitive RT followed by immunotherapy, consolidative SBRT of all tumor sites in combination with immunotherapy, and trials that incorporate surrogate immunotherapy-relevant biomarkers to assess earlier and more efficiently the impact of an intervention.”

The study was partly supported by a grant from the National Cancer Institute. Bristol-Myers Squibb provided the study drug and funded tumor staining.

Multiple study authors have financial ties to industry, including two with ties to Bristol-Myers Squibb. Both editorialists have ties to industry, including Dr. Seiwert’s ties to Bristol-Myers Squibb.

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

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The European PET-Boost trial finds that both of two strategies for delivering a radiation boost to locally advanced non–small cell lung cancer (NSCLC) tumors improve local control relative to that seen historically. Results were reported at the European Society for Radiology and Oncology 2020 Online Congress. 

“From previous studies, we know that local recurrences have an important negative impact on survival,” said presenting author Saskia A. Cooke, an MD, PhD candidate in the department of Radiation Oncology Research, the Netherlands Cancer Institute, Amsterdam.

In addition, research shows that, despite advances in drug therapy, the most common site of progression in this population is intrathoracic.

“These results further underline the need to develop treatment strategies which effectively prevent intrathoracic and local recurrences,” Ms. Cooke said.

PET-Boost is a multicenter, randomized trial that enrolled patients with inoperable stage II or III NSCLC and a primary tumor measuring 4 cm or greater.

“The study was a phase 2 ‘pick the winner’ trial, which, by design, does not compare the two arms to one another but to a historic rate of outcome,” Ms. Cooke explained.

The patients were randomized evenly to receive the standard 66 Gy of radiotherapy given in 24 fractions of 2.75 Gy with one of two dose-escalation strategies: a boost to the whole primary tumor or a boost to only the tumor area having high metabolic activity, with a maximum standard uptake value (SUVmax) of at least 50% on the pretreatment FDG-PET scan.

For each patient, both plans were created before randomization, with the dose escalated as high as possible up to an organ-at-risk constraint, Ms. Cooke noted.

“A key element is that the two plans were made isotoxic by equaling the mean lung dose, and in both arms, the dose was delivered integrated into the 24 fractions, so without prolongation of the overall treatment time,” she said.

The trial’s goal was to improve the 1-year rate of freedom from local failure from the 70% seen historically with conventional chemoradiotherapy to 85%.

The trial was stopped early because of slow accrual, after enrollment of 107 patients, Ms. Cooke reported. The large majority received concurrent or sequential chemotherapy with their radiotherapy.

With a median follow-up of 12.6 months for the endpoint, the 1-year rate of freedom from local failure as determined on centrally reviewed CT scans was 97% with the whole-tumor boost and 91% with the PET-directed boost. The 2-year rates were 89% and 82%, respectively.

With a median follow-up of 61 months for the endpoint, the 1-year rate of overall survival was 77% with the whole-tumor boost and 62% with the PET-directed boost. The 2-year rates were 46% and 43%, respectively.

The two boost strategies increased acute and late toxicity over that seen historically, but not to unacceptable levels, as reported previously (Radiother Oncol. 2019;131:166-73).

“In this PET-Boost trial, using hypofractionated personalized dose escalation led to a very good local control rate, which, in both arms, was more than 90% at 1 year,” Ms. Cooke summarized.

In fact, values compare favorably with those seen in the phase 3 RTOG 0617 trial using conventional chemoradiotherapy and dose escalation, even though patients in that trial had smaller tumors.

“Survival, especially in the group treated with the homogeneous boost, was actually similar to the RTOG 0617 high-dose arm and also quite similar to the 1-year survival in the placebo arm of the PACIFIC trial,” she added. The somewhat poorer survival at 2 years in PET-Boost was likely related, in part, to the large tumor volumes and the mediastinal radiation dose, she speculated.

The investigators are now evaluating specific sites of failure and extrathoracic recurrences, as well as assessing associations of toxicity with organ-at-risk doses and quality of life.

“While further results of the trial are awaited, so far, we do believe that in selected patients with locally advanced NSCLC, hypofractionated dose escalation to the tumor is a very important subject for future research,” Ms. Cooke said.

The investigators plan to carry the whole-tumor boost strategy forward because it yields similar efficacy but is easier to plan.

Not ready for prime time

“Overall, this study conceptually is well designed as it is forward thinking and uses imaging to personalize radiation treatment, going to higher doses to active areas of disease based on FDG-PET imaging,” Arya Amini, MD, assistant clinical professor in the department of radiation oncology, City of Hope Comprehensive Cancer Center, Duarte, Calif., said in an interview.

SOURCE: Lalezari F et al. ESTRO 2020. Abstract OC-0609.

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

The US Food and Drug Administration (FDA) has approved osimertinib (Tagrisso) as the first adjuvant treatment for adults with early-stage non–small cell lung cancer (NSCLC) bearing EGFR exon 19 deletions or exon 21 L858R mutations.

Osimertinib was first approved in the US in 2018 for the first-line treatment of patients with metastatic EGFR-mutated NSCLC.

With this new indication, “patients may be treated with this targeted therapy in an earlier and potentially more curative stage of non-small cell lung cancer,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release.

The expanded indication is based on results of the ADAURA clinical trial, which compared osimertinib with placebo following complete resection of localized or locally advanced NSCLC with negative margins. 

In the trial, adjuvant osimertinib reduced the relative risk of disease recurrence or death by 83% in patients with stage II and IIIA disease (hazard ratio [HR], 0.17; 95% CI, 0.12 - 0.23; P < .0001).

Disease-free survival (DFS) in the overall trial population of patients with stage IB-IIIA disease showed osimertinib reduced the risk of disease recurrence or death by 80% (HR, 0.20; 95% CI, 0.15 - 0.27; P < .0001).

At 2 years, 89% of patients treated with the targeted agent remained alive and disease free vs 52% on placebo after surgery. The safety and tolerability of osimertinib in the adjuvant setting was consistent with previous trials in the metastatic setting.

The trial of 682 patients was unblinded early and halted on the recommendation of the independent data-monitoring committee, because of the efficacy of osimertinib.

“If I were on the committee, I would have done the same thing. These are extraordinary results,” study investigator Roy S. Herbst, MD, PhD, chief of medical oncology at the Yale Cancer Center, New Haven, Connecticut, said at a press briefing prior to the study presentation at the American Society of Clinical Oncology’s (ASCO) virtual scientific program last spring.

In a Medscape commentary, Mark Kris, MD, of Memorial Sloan Kettering Cancer Center in New York City, said the data with osimertinib in the adjuvant setting are “important and practice-changing.”

“The potential for this drug to improve outcomes has been there for a long time. This phase 3 randomized trial presented at the plenary session of ASCO showed a more than doubling of disease-free survival at 2 years. It shows that we can use therapies in the earlier stages of disease,” Kris noted.

“This approval dispels the notion that treatment is over after surgery and chemotherapy, as the ADAURA results show that Tagrisso can dramatically change the course of this disease,” Dave Fredrickson, executive vice president, AstraZeneca oncology business unit, said in a news release.

Osimertinib had orphan drug status and breakthrough therapy designation for treatment of EGFR mutation-positive NSCLC.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

Earlier this week, Medscape spoke with Nora Disis, MD, about vaccinating cancer patients. Disis is a medical oncologist and director of both the Institute of Translational Health Sciences and the Cancer Vaccine Institute, the University of Washington, Seattle, Washington. As editor-in-chief of JAMA Oncology, she has watched COVID-19 developments in the oncology community over the past year.

Here are a few themes that Disis said oncologists should be aware of as vaccines eventually begin reaching cancer patients.

We should expect cancer patients to respond to vaccines. Historically, some believed that cancer patients would be unable to mount an immune response to vaccines. Data on other viral vaccines have shown otherwise. For example, there has been a long history of studies of flu vaccination in cancer patients, and in general, those vaccines confer protection. Likewise for pneumococcal vaccine, which, generally speaking, cancer patients should receive.

Special cases may include hematologic malignancies in which the immune system has been destroyed and profound immunosuppression occurs. Data on immunization during this immunosuppressed period are scarce, but what data are available suggest that once cancer patients are through this immunosuppressed period, they can be vaccinated successfully.

The type of vaccine will probably be important for cancer patients. Currently, there are 61 coronavirus vaccines in human clinical trials, and 17 have reached the final stages of testing. At least 85 preclinical vaccines are under active investigation in animals.

Both the Pfizer-BioNTech and Moderna COVID vaccines are mRNA type. There are many other types, including protein-based vaccines, viral vector vaccines based on adenoviruses, and inactivated or attenuated coronavirus vaccines.

The latter vaccines, particularly attenuated live virus vaccines, may not be a good choice for cancer patients. Especially in those with rapidly progressing disease or on chemotherapy, attenuated live viruses may cause a low-grade infection.

Incidentally, the technology used in the genetic, or mRNA, vaccines developed by both Pfizer-BioNTech and Moderna was initially developed for fighting cancer, and studies have shown that patients can generate immune responses to cancer-associated proteins with this type of vaccine.

These genetic vaccines could turn out to be the most effective for cancer patients, especially those with solid tumors.

Our understanding is very limited right now. Neither the Pfizer-BioNTech nor the Moderna early data discuss cancer patients. Two of the most important questions for cancer patients are dosing and booster scheduling. Potential defects in lymphocyte function among cancer patients may require unique initial dosing and booster schedules. In terms of timing, it is unclear how active therapy might affect a patient’s immune response to vaccination and whether vaccines should be timed with therapy cycles.

Vaccine access may depend on whether cancer patients are viewed as a vulnerable population. Those at higher risk for severe COVID-19 clearly have a greater need for vaccination. While there are data suggesting that cancer patients are at higher risk, they are a bit murky, in part because cancer patients are a heterogeneous group. For example, there are data suggesting that lung and blood cancer patients fare worse. There is also a suggestion that, like in the general population, COVID risk in cancer patients remains driven by comorbidities.

It is likely, then, that personalized risk factors such as type of cancer therapy, site of disease, and comorbidities will shape individual choices about vaccination among cancer patients.

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

Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).

Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.

However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.

The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.

These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.

“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.

Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”

To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.

The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).

The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
 

One in five people will develop cancer

The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.

Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.

Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.

“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.

The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.

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

Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).

Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.

However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.

The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.

These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.

“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.

Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”

To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.

The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).

The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
 

One in five people will develop cancer

The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.

Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.

Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.

“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.

The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.

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

Breast cancer now tops the list of the most commonly diagnosed cancers worldwide, surpassing lung cancer for the first time, according to the latest global cancer burden estimates from the International Agency for Research on Cancer (IARC).

Breast cancer among women accounted for 11.7% of the estimated 19.3 million new cancer cases in 2020 ― and about 25% of all cancer cases among women. Lung cancer accounted for 11.4% of new cases, reports the IARC, part of the World Health Organization.

However, lung cancer remains the leading overall cause of cancer mortality, accounting for 18.0% of 10 million cancer deaths. Breast cancer ranks fifth as a cause of cancer mortality, accounting for 1 of every 6 cancer deaths in women and 685,000 deaths overall (6.9%) in 2020, but it ranks first in incidence in 159 countries and first in mortality in 110 countries, the data show.

The increase in breast cancer cases is likely attributable to the effects of “marked changes in lifestyle, sociocultural contexts, and built environments” in many countries, says the IACR. These include delayed childbearing, having fewer children, increased rates of overweight and obesity, and decreasing levels of physical activity, the IACR explains in a press release.

These new data underscore the importance of focusing on cancer prevention, IARC Director Elisabete Weiderpass, MD, states in the press release.

“Effective interventions for prevention and early detection are available and must be integrated into cancer planning to control the predicted upsurge of this devastating disease,” she said.

Weiderpass also notes that the “overwhelming need for evidence-based and resource-stratified guidelines that support the phased implementation of breast cancer early detection and treatment into real-world practice.”

To that end, the WHO and the IARC will launch a global breast cancer initiative in 2021 to improve population-level outcomes through a focus on more timely diagnosis and comprehensive treatment, she adds.

The most common cancer diagnoses worldwide after breast cancer and lung cancer are colorectal cancer (10.0%), prostate cancer (7.3%), and stomach cancer (5.6%).

The leading causes of cancer deaths after lung cancer are colorectal cancer (9.4%), liver cancer (8.3%), stomach cancer (7.7%), and breast cancer among women.
 

One in five people will develop cancer

The IACR estimates that 1 in 5 people will develop cancer in their lifetime and that 1 in 8 men and 1 in 11 women will die from it.

Among women, breast cancer is the most common cancer type and the most common cause of cancer death. Colorectal cancer and lung cancer are the second and third most common cancer types and the third and second most common causes of cancer death, respectively.

Among men, lung cancer is the most common cancer type and the most common cause of cancer death. Prostate cancer and colorectal cancer are the second and third most common cancer types, and liver cancer and colorectal cancer are the second and third most common causes of cancer death.

“Worldwide, an estimated 28.4 million new cancer cases are projected to occur in 2040, a 47% increase from the estimated 19.3 million cases in 2020,” the IARC notes.

The agency derives its estimates from the GLOBOCAN 2020 database, which tracks 185 countries and 36 types of cancer and is accessible through the IARC Global Cancer Observatory.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Rechallenge with carboplatin plus etoposide is a “reasonable” second-line chemotherapy option for patients with relapsed small-cell lung cancer (SCLC), researchers reported in The Lancet Oncology.

In a phase 3 trial, carboplatin plus etoposide significantly prolonged progression-free survival (PFS), when compared with topotecan, in patients with advanced or relapsed, sensitive SCLC.

All patients had responded to first-line platinum plus etoposide, but they experienced relapse or progression 90 days or more after completing that treatment, according to study author Nathalie Baize, MD, of Angers University Hospital in France, and colleagues.

For this trial, Dr. Baize and colleagues enrolled 164 patients with advanced or relapsed SCLC. The median age of the 162 evaluable patients was 64 years, about two-thirds were men, and about 60% had an Eastern Cooperative Oncology Group performance status of 1.

The patients were randomized 1:1 to intravenous carboplatin (area under the curve 5 mg/mL per min on day 1) plus intravenous etoposide (100 mg/m² from day 1 to day 3) or to oral topotecan (2.3 mg/m² from day 1 to day 5 for six cycles). Primary prophylactic filgrastim was recommended for all patients in both treatment groups.
 

Results: Survival and adverse events

The median follow-up was 22.7 months. The median PFS was significantly longer in the combination therapy arm, at 4.7 months versus 2.7 months in the topotecan arm (stratified hazard ratio 0.57, P = .0041).

The median overall survival was similar in both arms, at 7.5 months in the carboplatin-etoposide arm and 7.4 months in the topotecan arm.

Patients in the carboplatin-etoposide arm had a significantly higher objective response rate, at 49% versus 25% in the topotecan arm (P = .0024).

The most common grade 3-4 adverse events (in the topotecan and combination arms, respectively) were neutropenia (22% vs. 14%), thrombocytopenia (36% vs. 31%), and anemia (21% vs. 25%).

Serious adverse events with hospitalization were reported in 37% of patients in the carboplatin-etoposide arm 43% in the topotecan arm. Febrile neutropenia with sepsis led to two treatment-related deaths in the topotecan group but none in the carboplatin-etoposide group.
 

Reasonable option for some

Based on the results of this trial, Dr. Baize and colleagues concluded that carboplatin-etoposide rechallenge “can be considered a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer.”

However, while this trial was enrolling patients, immunotherapy and chemotherapy combinations became the standard of care in SCLC, Oscar Arrieta, MD, of Instituto Nacional de Cancerología in Mexico City, and colleagues noted in a related editorial.

Therefore, “reasonable doubts emerge regarding the application of this strategy in patients receiving immunotherapy,” Dr. Arrieta and colleagues wrote.

The editorialists urged conduct of a randomized trial to evaluate rechallenge with carboplatin plus etoposide versus lurbinectedin, which was approved earlier this year by the Food and Drug Administration for the treatment of sensitive and resistant relapsed SCLC.

Commenting on the choice between a platinum-etoposide combination and lurbinectedin, Sarah Goldberg, MD, of Yale University, New Haven, Conn., noted that she and her colleagues have been using the chemotherapy combination for several years.

“This trial confirms that practice and that it’s still a reasonable option for some patients,” Dr. Goldberg said in an interview.

For patients who had a very good first-line response to platinum-etoposide, longer than 180 days (even longer than the 90-day standard in the current trial), she said, “it seems like a rechallenge with platinum-etoposide would potentially be even more effective, and I’d save lurbinectedin for a later line.

“With refractory disease, less than 90 days, I would consider lurbinectedin,” Dr. Goldberg said.

This study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). The researchers disclosed relationships with Pfizer, Roche, AbbVie, and many other companies. Dr. Arrieta disclosed relationships with AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Merck, Pfizer, and Bristol-Myers Squibb. The other editorialists declared no competing interests. Dr. Goldberg disclosed relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, and Regeneron.
 

SOURCE: Baize N et al. Lancet Oncol. 2020;21:1224-33.

Rechallenge with carboplatin plus etoposide is a “reasonable” second-line chemotherapy option for patients with relapsed small-cell lung cancer (SCLC), researchers reported in The Lancet Oncology.

In a phase 3 trial, carboplatin plus etoposide significantly prolonged progression-free survival (PFS), when compared with topotecan, in patients with advanced or relapsed, sensitive SCLC.

All patients had responded to first-line platinum plus etoposide, but they experienced relapse or progression 90 days or more after completing that treatment, according to study author Nathalie Baize, MD, of Angers University Hospital in France, and colleagues.

For this trial, Dr. Baize and colleagues enrolled 164 patients with advanced or relapsed SCLC. The median age of the 162 evaluable patients was 64 years, about two-thirds were men, and about 60% had an Eastern Cooperative Oncology Group performance status of 1.

The patients were randomized 1:1 to intravenous carboplatin (area under the curve 5 mg/mL per min on day 1) plus intravenous etoposide (100 mg/m² from day 1 to day 3) or to oral topotecan (2.3 mg/m² from day 1 to day 5 for six cycles). Primary prophylactic filgrastim was recommended for all patients in both treatment groups.
 

Results: Survival and adverse events

The median follow-up was 22.7 months. The median PFS was significantly longer in the combination therapy arm, at 4.7 months versus 2.7 months in the topotecan arm (stratified hazard ratio 0.57, P = .0041).

The median overall survival was similar in both arms, at 7.5 months in the carboplatin-etoposide arm and 7.4 months in the topotecan arm.

Patients in the carboplatin-etoposide arm had a significantly higher objective response rate, at 49% versus 25% in the topotecan arm (P = .0024).

The most common grade 3-4 adverse events (in the topotecan and combination arms, respectively) were neutropenia (22% vs. 14%), thrombocytopenia (36% vs. 31%), and anemia (21% vs. 25%).

Serious adverse events with hospitalization were reported in 37% of patients in the carboplatin-etoposide arm 43% in the topotecan arm. Febrile neutropenia with sepsis led to two treatment-related deaths in the topotecan group but none in the carboplatin-etoposide group.
 

Reasonable option for some

Based on the results of this trial, Dr. Baize and colleagues concluded that carboplatin-etoposide rechallenge “can be considered a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer.”

However, while this trial was enrolling patients, immunotherapy and chemotherapy combinations became the standard of care in SCLC, Oscar Arrieta, MD, of Instituto Nacional de Cancerología in Mexico City, and colleagues noted in a related editorial.

Therefore, “reasonable doubts emerge regarding the application of this strategy in patients receiving immunotherapy,” Dr. Arrieta and colleagues wrote.

The editorialists urged conduct of a randomized trial to evaluate rechallenge with carboplatin plus etoposide versus lurbinectedin, which was approved earlier this year by the Food and Drug Administration for the treatment of sensitive and resistant relapsed SCLC.

Commenting on the choice between a platinum-etoposide combination and lurbinectedin, Sarah Goldberg, MD, of Yale University, New Haven, Conn., noted that she and her colleagues have been using the chemotherapy combination for several years.

“This trial confirms that practice and that it’s still a reasonable option for some patients,” Dr. Goldberg said in an interview.

For patients who had a very good first-line response to platinum-etoposide, longer than 180 days (even longer than the 90-day standard in the current trial), she said, “it seems like a rechallenge with platinum-etoposide would potentially be even more effective, and I’d save lurbinectedin for a later line.

“With refractory disease, less than 90 days, I would consider lurbinectedin,” Dr. Goldberg said.

This study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). The researchers disclosed relationships with Pfizer, Roche, AbbVie, and many other companies. Dr. Arrieta disclosed relationships with AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Merck, Pfizer, and Bristol-Myers Squibb. The other editorialists declared no competing interests. Dr. Goldberg disclosed relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, and Regeneron.
 

SOURCE: Baize N et al. Lancet Oncol. 2020;21:1224-33.

Rechallenge with carboplatin plus etoposide is a “reasonable” second-line chemotherapy option for patients with relapsed small-cell lung cancer (SCLC), researchers reported in The Lancet Oncology.

In a phase 3 trial, carboplatin plus etoposide significantly prolonged progression-free survival (PFS), when compared with topotecan, in patients with advanced or relapsed, sensitive SCLC.

All patients had responded to first-line platinum plus etoposide, but they experienced relapse or progression 90 days or more after completing that treatment, according to study author Nathalie Baize, MD, of Angers University Hospital in France, and colleagues.

For this trial, Dr. Baize and colleagues enrolled 164 patients with advanced or relapsed SCLC. The median age of the 162 evaluable patients was 64 years, about two-thirds were men, and about 60% had an Eastern Cooperative Oncology Group performance status of 1.

The patients were randomized 1:1 to intravenous carboplatin (area under the curve 5 mg/mL per min on day 1) plus intravenous etoposide (100 mg/m² from day 1 to day 3) or to oral topotecan (2.3 mg/m² from day 1 to day 5 for six cycles). Primary prophylactic filgrastim was recommended for all patients in both treatment groups.
 

Results: Survival and adverse events

The median follow-up was 22.7 months. The median PFS was significantly longer in the combination therapy arm, at 4.7 months versus 2.7 months in the topotecan arm (stratified hazard ratio 0.57, P = .0041).

The median overall survival was similar in both arms, at 7.5 months in the carboplatin-etoposide arm and 7.4 months in the topotecan arm.

Patients in the carboplatin-etoposide arm had a significantly higher objective response rate, at 49% versus 25% in the topotecan arm (P = .0024).

The most common grade 3-4 adverse events (in the topotecan and combination arms, respectively) were neutropenia (22% vs. 14%), thrombocytopenia (36% vs. 31%), and anemia (21% vs. 25%).

Serious adverse events with hospitalization were reported in 37% of patients in the carboplatin-etoposide arm 43% in the topotecan arm. Febrile neutropenia with sepsis led to two treatment-related deaths in the topotecan group but none in the carboplatin-etoposide group.
 

Reasonable option for some

Based on the results of this trial, Dr. Baize and colleagues concluded that carboplatin-etoposide rechallenge “can be considered a reasonable second-line chemotherapy option for patients with sensitive relapsed small-cell lung cancer.”

However, while this trial was enrolling patients, immunotherapy and chemotherapy combinations became the standard of care in SCLC, Oscar Arrieta, MD, of Instituto Nacional de Cancerología in Mexico City, and colleagues noted in a related editorial.

Therefore, “reasonable doubts emerge regarding the application of this strategy in patients receiving immunotherapy,” Dr. Arrieta and colleagues wrote.

The editorialists urged conduct of a randomized trial to evaluate rechallenge with carboplatin plus etoposide versus lurbinectedin, which was approved earlier this year by the Food and Drug Administration for the treatment of sensitive and resistant relapsed SCLC.

Commenting on the choice between a platinum-etoposide combination and lurbinectedin, Sarah Goldberg, MD, of Yale University, New Haven, Conn., noted that she and her colleagues have been using the chemotherapy combination for several years.

“This trial confirms that practice and that it’s still a reasonable option for some patients,” Dr. Goldberg said in an interview.

For patients who had a very good first-line response to platinum-etoposide, longer than 180 days (even longer than the 90-day standard in the current trial), she said, “it seems like a rechallenge with platinum-etoposide would potentially be even more effective, and I’d save lurbinectedin for a later line.

“With refractory disease, less than 90 days, I would consider lurbinectedin,” Dr. Goldberg said.

This study was funded by Amgen and the French Lung Cancer Group (Groupe Français de Pneumo-Cancérologie). The researchers disclosed relationships with Pfizer, Roche, AbbVie, and many other companies. Dr. Arrieta disclosed relationships with AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Merck, Pfizer, and Bristol-Myers Squibb. The other editorialists declared no competing interests. Dr. Goldberg disclosed relationships with AstraZeneca, Boehringer Ingelheim, Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, Blueprint Medicine, Sanofi Genzyme, Daiichi Sankyo, and Regeneron.
 

SOURCE: Baize N et al. Lancet Oncol. 2020;21:1224-33.

Every medical oncologist who has described a combination chemotherapy regimen to a patient with advanced cancer has likely been asked whether the benefits of tumor shrinkage, disease-free survival (DFS), and overall survival are worth the risks of adverse events (AEs).

Single-agent immunotherapy and, more recently, combinations of immunotherapy drugs have been approved for a variety of metastatic tumors. In general, combination immunotherapy regimens have more AEs and a higher frequency of premature treatment discontinuation for toxicity.

Michael Postow, MD, of Memorial Sloan Kettering Cancer Center in New York, reflected on new ways to evaluate the benefits and risks of immunotherapy combinations during a plenary session on novel combinations at the American Association for Cancer Research’s Virtual Special Conference on Tumor Immunology and Immunotherapy.
 

Potential targets

As with chemotherapy drugs, immunotherapy combinations make the most sense when drugs targeting independent processes are employed.

As described in a paper published in Nature in 2011, the process for recruiting the immune system to combat cancer is as follows:

• Dendritic cells must sample antigens derived from the tumor.
• The dendritic cells must receive an activation signal so they promote immunity rather than tolerance.
• The tumor antigen–loaded dendritic cells need to generate protective T-cell responses, instead of T-regulatory responses, in lymphoid tissues.
• Cancer antigen–specific T cells must enter tumor tissues.
• Tumor-derived mechanisms for promoting immunosuppression need to be circumvented.

Since each step in the cascade is a potential therapeutic target, there are large numbers of potential drug combinations.
 

Measuring impact

Conventional measurements of tumor response may not be adequately sensitive to the impact from immunotherapy drugs. A case in point is sipuleucel-T, which is approved to treat advanced prostate cancer.

In the pivotal phase 3 trial, only 1 of 341 patients receiving sipuleucel-T achieved a partial response by RECIST criteria. Only 2.6% of patients had a 50% reduction in prostate-specific antigen levels. Nonetheless, a 4.1-month improvement in median overall survival was achieved. These results were published in the New England Journal of Medicine.

The discrepancy between tumor shrinkage and survival benefit for immunotherapy is not unexpected. As many as 10% of patients treated with ipilimumab (ipi) for stage IV malignant melanoma have progressive disease by tumor size but experience prolongation of survival, according to guidelines published in Clinical Cancer Research.

Accurate assessment of the ultimate efficacy of immunotherapy over time would benefit patients and clinicians since immune checkpoint inhibitors are often administered for several years, are financially costly, and treatment-associated AEs emerge unpredictably at any time.

Curtailing the duration of ineffective treatment could be valuable from many perspectives.
 

Immunotherapy combinations in metastatic melanoma

In the CheckMate 067 study, there was an improvement in response, progression-free survival (PFS), and overall survival for nivolumab (nivo) plus ipi or nivo alone, in comparison with ipi alone, in patients with advanced melanoma. Initial results from this trial were published in the New England Journal of Medicine in 2017.

At a minimum follow-up of 60 months, the 5-year overall survival was 52% for the nivo/ipi regimen, 44% for nivo alone, and 26% for ipi alone. These results were published in the New England Journal of Medicine in 2019.

The trial was not statistically powered to conclude whether the overall survival for the combination was superior to that of single-agent nivo alone, but both nivo regimens were superior to ipi alone.

Unfortunately, the combination also produced the highest treatment-related AE rates – 59% with nivo/ipi, 23% with nivo, and 28% with ipi in 2019. In the 2017 report, the combination regimen had more than twice as many premature treatment discontinuations as the other two study arms.

Is there a better way to quantify the risk-benefit ratio and explain it to patients?
 

Alternative strategies for assessing benefit: Treatment-free survival

Researchers have proposed treatment-free survival (TFS) as a potential new metric to characterize not only antitumor activity but also toxicity experienced after the cessation of therapy and before initiation of subsequent systemic therapy or death.

TFS is defined as the area between Kaplan-Meier curves from immunotherapy cessation until the reinitiation of systemic therapy or death. All patients who began immunotherapy are included – not just those achieving response or concluding a predefined number of cycles of treatment.

The curves can be partitioned into states with and without toxicity to establish a unique endpoint: time to cessation of both immunotherapy and toxicity.

Researchers conducted a pooled analysis of 3-year follow-up data from the 1,077 patients who participated in CheckMate 069, testing nivo/ipi versus nivo alone, and CheckMate 067, comparing nivo/ipi, nivo alone, and ipi alone. The results were published in the Journal of Clinical Oncology.

The TFS without grade 3 or higher AEs was 28% for nivo/ipi, 11% for nivo alone, and 23% for ipi alone. The restricted mean time without either treatment or grade 3 or greater AEs was 10.1 months, 4.1 months, and 8.5 months, respectively.

TFS incentivizes the use of regimens that have:

• A short duration of treatment
• Prolonged time to subsequent therapy or death
• Only mild AEs of brief duration.

A higher TFS corresponds with the goals that patients and their providers would have for a treatment regimen.
 

Adaptive models provide clues about benefit from extended therapy

In contrast to cytotoxic chemotherapy and molecularly targeted agents, benefit from immune-targeted therapy can deepen and persist after treatment discontinuation.

In advanced melanoma, researchers observed that overall survival was similar for patients who discontinued nivo/ipi because of AEs during the induction phase of treatment and those who did not. These results were published in the Journal of Clinical Oncology.

This observation has led to an individualized, adaptive approach to de-escalating combination immunotherapy, described in Clinical Cancer Research. The approach is dubbed “SMART,” which stands for sequential multiple assignment randomized trial designs.

With the SMART approach, each stage of a trial corresponds to an important treatment decision point. The goal is to define the population of patients who can safely discontinue treatment based on response, rather than doing so after the development of AEs.

In the Adapt-IT prospective study, 60 patients with advanced melanoma with poor prognostic features were given two doses of nivo/ipi followed by a CT scan at week 6. They were triaged to stopping ipi and proceeding with maintenance therapy with nivo alone or continuing the combination for an additional two cycles of treatment. Results from this trial were presented at ASCO 2020 (abstract 10003).

The investigators found that 68% of patients had no tumor burden increase at week 6 and could discontinue ipi. For those patients, their response rate of 57% approached the expected results from a full course of ipi.

At median follow-up of 22.3 months, median response duration, PFS, and overall survival had not been reached for the responders who received an abbreviated course of the combination regimen.

There were two observations that suggested the first two cycles of treatment drove not only toxicity but also tumor control:

• The rate of grade 3-4 toxicity from only two cycles was high (57%).
• Of the 19 patients (32% of the original 60 patients) who had progressive disease after two cycles of nivo/ipi, there were no responders with continued therapy.

Dr. Postow commented that, in correlative studies conducted as part of Adapt-IT, the Ki-67 of CD8-positive T cells increased after the initial dose of nivo/ipi. However, proliferation did not continue with subsequent cycles (that is, Ki-67 did not continue to rise).

When they examined markers of T-cell stimulation such as inducible costimulator of CD8-positive T cells, the researchers observed the same effect. The “immune boost” occurred with cycle one but not after subsequent doses of the nivo/ipi combination.

Although unproven in clinical trials at this time, these data suggest that response and risks of toxicity may not support giving patients more than one cycle of combination treatment.
 

More nuanced ways of assessing tumor growth

Dr. Postow noted that judgment about treatment effects over time are often made by displaying spider plots of changes from baseline tumor size from “time zero” – the time at which combination therapy is commenced.

He speculated that it might be worthwhile to give a dose or two of immune-targeted monotherapy (such as a PD-1 or PD-L1 inhibitor alone) before time zero, measure tumor growth prior to and after the single agent, and reserve using combination immunotherapy only for those patients who do not experience a dampening of the growth curve.

Patients whose tumor growth kinetics are improved with single-agent treatment could be spared the additional toxicity (and uncertain additive benefit) from the second agent.
 

Treatment optimization: More than ‘messaging’

Oncology practice has passed through a long era of “more is better,” an era that gave rise to intensive cytotoxic chemotherapy for hematologic and solid tumors in the metastatic and adjuvant settings. In some cases, that approach proved to be curative, but not in all.

More recently, because of better staging, improved outcomes with newer technology and treatments, and concern about immediate- and late-onset health risks, there has been an effort to deintensify therapy when it can be done safely.

Once a treatment regimen and treatment duration become established, however, patients and their physicians are reluctant to deintensity therapy.

Dr. Postow’s presentation demonstrated that, with regard to immunotherapy combinations – as in other realms of medical practice – science can lead the way to treatment optimization for individual patients.

We have the potential to reassure patients that treatment de-escalation is a rational and personalized component of treatment optimization through the combination of:

• Identifying new endpoints to quantify treatment benefits and risks.
• SMART trial designs.
• Innovative ways to assess tumor response during each phase of a treatment course.

Precision assessment of immunotherapy effect in individual patients can be a key part of precision medicine.

Dr. Postow disclosed relationships with Aduro, Array BioPharma, Bristol Myers Squibb, Eisai, Incyte, Infinity, Merck, NewLink Genetics, Novartis, and RGenix.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Every medical oncologist who has described a combination chemotherapy regimen to a patient with advanced cancer has likely been asked whether the benefits of tumor shrinkage, disease-free survival (DFS), and overall survival are worth the risks of adverse events (AEs).

Single-agent immunotherapy and, more recently, combinations of immunotherapy drugs have been approved for a variety of metastatic tumors. In general, combination immunotherapy regimens have more AEs and a higher frequency of premature treatment discontinuation for toxicity.

Michael Postow, MD, of Memorial Sloan Kettering Cancer Center in New York, reflected on new ways to evaluate the benefits and risks of immunotherapy combinations during a plenary session on novel combinations at the American Association for Cancer Research’s Virtual Special Conference on Tumor Immunology and Immunotherapy.
 

Potential targets

As with chemotherapy drugs, immunotherapy combinations make the most sense when drugs targeting independent processes are employed.

As described in a paper published in Nature in 2011, the process for recruiting the immune system to combat cancer is as follows:

• Dendritic cells must sample antigens derived from the tumor.
• The dendritic cells must receive an activation signal so they promote immunity rather than tolerance.
• The tumor antigen–loaded dendritic cells need to generate protective T-cell responses, instead of T-regulatory responses, in lymphoid tissues.
• Cancer antigen–specific T cells must enter tumor tissues.
• Tumor-derived mechanisms for promoting immunosuppression need to be circumvented.

Since each step in the cascade is a potential therapeutic target, there are large numbers of potential drug combinations.
 

Measuring impact

Conventional measurements of tumor response may not be adequately sensitive to the impact from immunotherapy drugs. A case in point is sipuleucel-T, which is approved to treat advanced prostate cancer.

In the pivotal phase 3 trial, only 1 of 341 patients receiving sipuleucel-T achieved a partial response by RECIST criteria. Only 2.6% of patients had a 50% reduction in prostate-specific antigen levels. Nonetheless, a 4.1-month improvement in median overall survival was achieved. These results were published in the New England Journal of Medicine.

The discrepancy between tumor shrinkage and survival benefit for immunotherapy is not unexpected. As many as 10% of patients treated with ipilimumab (ipi) for stage IV malignant melanoma have progressive disease by tumor size but experience prolongation of survival, according to guidelines published in Clinical Cancer Research.

Accurate assessment of the ultimate efficacy of immunotherapy over time would benefit patients and clinicians since immune checkpoint inhibitors are often administered for several years, are financially costly, and treatment-associated AEs emerge unpredictably at any time.

Curtailing the duration of ineffective treatment could be valuable from many perspectives.
 

Immunotherapy combinations in metastatic melanoma

In the CheckMate 067 study, there was an improvement in response, progression-free survival (PFS), and overall survival for nivolumab (nivo) plus ipi or nivo alone, in comparison with ipi alone, in patients with advanced melanoma. Initial results from this trial were published in the New England Journal of Medicine in 2017.

At a minimum follow-up of 60 months, the 5-year overall survival was 52% for the nivo/ipi regimen, 44% for nivo alone, and 26% for ipi alone. These results were published in the New England Journal of Medicine in 2019.

The trial was not statistically powered to conclude whether the overall survival for the combination was superior to that of single-agent nivo alone, but both nivo regimens were superior to ipi alone.

Unfortunately, the combination also produced the highest treatment-related AE rates – 59% with nivo/ipi, 23% with nivo, and 28% with ipi in 2019. In the 2017 report, the combination regimen had more than twice as many premature treatment discontinuations as the other two study arms.

Is there a better way to quantify the risk-benefit ratio and explain it to patients?
 

Alternative strategies for assessing benefit: Treatment-free survival

Researchers have proposed treatment-free survival (TFS) as a potential new metric to characterize not only antitumor activity but also toxicity experienced after the cessation of therapy and before initiation of subsequent systemic therapy or death.

TFS is defined as the area between Kaplan-Meier curves from immunotherapy cessation until the reinitiation of systemic therapy or death. All patients who began immunotherapy are included – not just those achieving response or concluding a predefined number of cycles of treatment.

The curves can be partitioned into states with and without toxicity to establish a unique endpoint: time to cessation of both immunotherapy and toxicity.

Researchers conducted a pooled analysis of 3-year follow-up data from the 1,077 patients who participated in CheckMate 069, testing nivo/ipi versus nivo alone, and CheckMate 067, comparing nivo/ipi, nivo alone, and ipi alone. The results were published in the Journal of Clinical Oncology.

The TFS without grade 3 or higher AEs was 28% for nivo/ipi, 11% for nivo alone, and 23% for ipi alone. The restricted mean time without either treatment or grade 3 or greater AEs was 10.1 months, 4.1 months, and 8.5 months, respectively.

TFS incentivizes the use of regimens that have:

• A short duration of treatment
• Prolonged time to subsequent therapy or death
• Only mild AEs of brief duration.

A higher TFS corresponds with the goals that patients and their providers would have for a treatment regimen.
 

Adaptive models provide clues about benefit from extended therapy

In contrast to cytotoxic chemotherapy and molecularly targeted agents, benefit from immune-targeted therapy can deepen and persist after treatment discontinuation.

In advanced melanoma, researchers observed that overall survival was similar for patients who discontinued nivo/ipi because of AEs during the induction phase of treatment and those who did not. These results were published in the Journal of Clinical Oncology.

This observation has led to an individualized, adaptive approach to de-escalating combination immunotherapy, described in Clinical Cancer Research. The approach is dubbed “SMART,” which stands for sequential multiple assignment randomized trial designs.

With the SMART approach, each stage of a trial corresponds to an important treatment decision point. The goal is to define the population of patients who can safely discontinue treatment based on response, rather than doing so after the development of AEs.

In the Adapt-IT prospective study, 60 patients with advanced melanoma with poor prognostic features were given two doses of nivo/ipi followed by a CT scan at week 6. They were triaged to stopping ipi and proceeding with maintenance therapy with nivo alone or continuing the combination for an additional two cycles of treatment. Results from this trial were presented at ASCO 2020 (abstract 10003).

The investigators found that 68% of patients had no tumor burden increase at week 6 and could discontinue ipi. For those patients, their response rate of 57% approached the expected results from a full course of ipi.

At median follow-up of 22.3 months, median response duration, PFS, and overall survival had not been reached for the responders who received an abbreviated course of the combination regimen.

There were two observations that suggested the first two cycles of treatment drove not only toxicity but also tumor control:

• The rate of grade 3-4 toxicity from only two cycles was high (57%).
• Of the 19 patients (32% of the original 60 patients) who had progressive disease after two cycles of nivo/ipi, there were no responders with continued therapy.

Dr. Postow commented that, in correlative studies conducted as part of Adapt-IT, the Ki-67 of CD8-positive T cells increased after the initial dose of nivo/ipi. However, proliferation did not continue with subsequent cycles (that is, Ki-67 did not continue to rise).

When they examined markers of T-cell stimulation such as inducible costimulator of CD8-positive T cells, the researchers observed the same effect. The “immune boost” occurred with cycle one but not after subsequent doses of the nivo/ipi combination.

Although unproven in clinical trials at this time, these data suggest that response and risks of toxicity may not support giving patients more than one cycle of combination treatment.
 

More nuanced ways of assessing tumor growth

Dr. Postow noted that judgment about treatment effects over time are often made by displaying spider plots of changes from baseline tumor size from “time zero” – the time at which combination therapy is commenced.

He speculated that it might be worthwhile to give a dose or two of immune-targeted monotherapy (such as a PD-1 or PD-L1 inhibitor alone) before time zero, measure tumor growth prior to and after the single agent, and reserve using combination immunotherapy only for those patients who do not experience a dampening of the growth curve.

Patients whose tumor growth kinetics are improved with single-agent treatment could be spared the additional toxicity (and uncertain additive benefit) from the second agent.
 

Treatment optimization: More than ‘messaging’

Oncology practice has passed through a long era of “more is better,” an era that gave rise to intensive cytotoxic chemotherapy for hematologic and solid tumors in the metastatic and adjuvant settings. In some cases, that approach proved to be curative, but not in all.

More recently, because of better staging, improved outcomes with newer technology and treatments, and concern about immediate- and late-onset health risks, there has been an effort to deintensify therapy when it can be done safely.

Once a treatment regimen and treatment duration become established, however, patients and their physicians are reluctant to deintensity therapy.

Dr. Postow’s presentation demonstrated that, with regard to immunotherapy combinations – as in other realms of medical practice – science can lead the way to treatment optimization for individual patients.

We have the potential to reassure patients that treatment de-escalation is a rational and personalized component of treatment optimization through the combination of:

• Identifying new endpoints to quantify treatment benefits and risks.
• SMART trial designs.
• Innovative ways to assess tumor response during each phase of a treatment course.

Precision assessment of immunotherapy effect in individual patients can be a key part of precision medicine.

Dr. Postow disclosed relationships with Aduro, Array BioPharma, Bristol Myers Squibb, Eisai, Incyte, Infinity, Merck, NewLink Genetics, Novartis, and RGenix.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Every medical oncologist who has described a combination chemotherapy regimen to a patient with advanced cancer has likely been asked whether the benefits of tumor shrinkage, disease-free survival (DFS), and overall survival are worth the risks of adverse events (AEs).

Single-agent immunotherapy and, more recently, combinations of immunotherapy drugs have been approved for a variety of metastatic tumors. In general, combination immunotherapy regimens have more AEs and a higher frequency of premature treatment discontinuation for toxicity.

Michael Postow, MD, of Memorial Sloan Kettering Cancer Center in New York, reflected on new ways to evaluate the benefits and risks of immunotherapy combinations during a plenary session on novel combinations at the American Association for Cancer Research’s Virtual Special Conference on Tumor Immunology and Immunotherapy.
 

Potential targets

As with chemotherapy drugs, immunotherapy combinations make the most sense when drugs targeting independent processes are employed.

As described in a paper published in Nature in 2011, the process for recruiting the immune system to combat cancer is as follows:

• Dendritic cells must sample antigens derived from the tumor.
• The dendritic cells must receive an activation signal so they promote immunity rather than tolerance.
• The tumor antigen–loaded dendritic cells need to generate protective T-cell responses, instead of T-regulatory responses, in lymphoid tissues.
• Cancer antigen–specific T cells must enter tumor tissues.
• Tumor-derived mechanisms for promoting immunosuppression need to be circumvented.

Since each step in the cascade is a potential therapeutic target, there are large numbers of potential drug combinations.
 

Measuring impact

Conventional measurements of tumor response may not be adequately sensitive to the impact from immunotherapy drugs. A case in point is sipuleucel-T, which is approved to treat advanced prostate cancer.

In the pivotal phase 3 trial, only 1 of 341 patients receiving sipuleucel-T achieved a partial response by RECIST criteria. Only 2.6% of patients had a 50% reduction in prostate-specific antigen levels. Nonetheless, a 4.1-month improvement in median overall survival was achieved. These results were published in the New England Journal of Medicine.

The discrepancy between tumor shrinkage and survival benefit for immunotherapy is not unexpected. As many as 10% of patients treated with ipilimumab (ipi) for stage IV malignant melanoma have progressive disease by tumor size but experience prolongation of survival, according to guidelines published in Clinical Cancer Research.

Accurate assessment of the ultimate efficacy of immunotherapy over time would benefit patients and clinicians since immune checkpoint inhibitors are often administered for several years, are financially costly, and treatment-associated AEs emerge unpredictably at any time.

Curtailing the duration of ineffective treatment could be valuable from many perspectives.
 

Immunotherapy combinations in metastatic melanoma

In the CheckMate 067 study, there was an improvement in response, progression-free survival (PFS), and overall survival for nivolumab (nivo) plus ipi or nivo alone, in comparison with ipi alone, in patients with advanced melanoma. Initial results from this trial were published in the New England Journal of Medicine in 2017.

At a minimum follow-up of 60 months, the 5-year overall survival was 52% for the nivo/ipi regimen, 44% for nivo alone, and 26% for ipi alone. These results were published in the New England Journal of Medicine in 2019.

The trial was not statistically powered to conclude whether the overall survival for the combination was superior to that of single-agent nivo alone, but both nivo regimens were superior to ipi alone.

Unfortunately, the combination also produced the highest treatment-related AE rates – 59% with nivo/ipi, 23% with nivo, and 28% with ipi in 2019. In the 2017 report, the combination regimen had more than twice as many premature treatment discontinuations as the other two study arms.

Is there a better way to quantify the risk-benefit ratio and explain it to patients?
 

Alternative strategies for assessing benefit: Treatment-free survival

Researchers have proposed treatment-free survival (TFS) as a potential new metric to characterize not only antitumor activity but also toxicity experienced after the cessation of therapy and before initiation of subsequent systemic therapy or death.

TFS is defined as the area between Kaplan-Meier curves from immunotherapy cessation until the reinitiation of systemic therapy or death. All patients who began immunotherapy are included – not just those achieving response or concluding a predefined number of cycles of treatment.

The curves can be partitioned into states with and without toxicity to establish a unique endpoint: time to cessation of both immunotherapy and toxicity.

Researchers conducted a pooled analysis of 3-year follow-up data from the 1,077 patients who participated in CheckMate 069, testing nivo/ipi versus nivo alone, and CheckMate 067, comparing nivo/ipi, nivo alone, and ipi alone. The results were published in the Journal of Clinical Oncology.

The TFS without grade 3 or higher AEs was 28% for nivo/ipi, 11% for nivo alone, and 23% for ipi alone. The restricted mean time without either treatment or grade 3 or greater AEs was 10.1 months, 4.1 months, and 8.5 months, respectively.

TFS incentivizes the use of regimens that have:

• A short duration of treatment
• Prolonged time to subsequent therapy or death
• Only mild AEs of brief duration.

A higher TFS corresponds with the goals that patients and their providers would have for a treatment regimen.
 

Adaptive models provide clues about benefit from extended therapy

In contrast to cytotoxic chemotherapy and molecularly targeted agents, benefit from immune-targeted therapy can deepen and persist after treatment discontinuation.

In advanced melanoma, researchers observed that overall survival was similar for patients who discontinued nivo/ipi because of AEs during the induction phase of treatment and those who did not. These results were published in the Journal of Clinical Oncology.

This observation has led to an individualized, adaptive approach to de-escalating combination immunotherapy, described in Clinical Cancer Research. The approach is dubbed “SMART,” which stands for sequential multiple assignment randomized trial designs.

With the SMART approach, each stage of a trial corresponds to an important treatment decision point. The goal is to define the population of patients who can safely discontinue treatment based on response, rather than doing so after the development of AEs.

In the Adapt-IT prospective study, 60 patients with advanced melanoma with poor prognostic features were given two doses of nivo/ipi followed by a CT scan at week 6. They were triaged to stopping ipi and proceeding with maintenance therapy with nivo alone or continuing the combination for an additional two cycles of treatment. Results from this trial were presented at ASCO 2020 (abstract 10003).

The investigators found that 68% of patients had no tumor burden increase at week 6 and could discontinue ipi. For those patients, their response rate of 57% approached the expected results from a full course of ipi.

At median follow-up of 22.3 months, median response duration, PFS, and overall survival had not been reached for the responders who received an abbreviated course of the combination regimen.

There were two observations that suggested the first two cycles of treatment drove not only toxicity but also tumor control:

• The rate of grade 3-4 toxicity from only two cycles was high (57%).
• Of the 19 patients (32% of the original 60 patients) who had progressive disease after two cycles of nivo/ipi, there were no responders with continued therapy.

Dr. Postow commented that, in correlative studies conducted as part of Adapt-IT, the Ki-67 of CD8-positive T cells increased after the initial dose of nivo/ipi. However, proliferation did not continue with subsequent cycles (that is, Ki-67 did not continue to rise).

When they examined markers of T-cell stimulation such as inducible costimulator of CD8-positive T cells, the researchers observed the same effect. The “immune boost” occurred with cycle one but not after subsequent doses of the nivo/ipi combination.

Although unproven in clinical trials at this time, these data suggest that response and risks of toxicity may not support giving patients more than one cycle of combination treatment.
 

More nuanced ways of assessing tumor growth

Dr. Postow noted that judgment about treatment effects over time are often made by displaying spider plots of changes from baseline tumor size from “time zero” – the time at which combination therapy is commenced.

He speculated that it might be worthwhile to give a dose or two of immune-targeted monotherapy (such as a PD-1 or PD-L1 inhibitor alone) before time zero, measure tumor growth prior to and after the single agent, and reserve using combination immunotherapy only for those patients who do not experience a dampening of the growth curve.

Patients whose tumor growth kinetics are improved with single-agent treatment could be spared the additional toxicity (and uncertain additive benefit) from the second agent.
 

Treatment optimization: More than ‘messaging’

Oncology practice has passed through a long era of “more is better,” an era that gave rise to intensive cytotoxic chemotherapy for hematologic and solid tumors in the metastatic and adjuvant settings. In some cases, that approach proved to be curative, but not in all.

More recently, because of better staging, improved outcomes with newer technology and treatments, and concern about immediate- and late-onset health risks, there has been an effort to deintensify therapy when it can be done safely.

Once a treatment regimen and treatment duration become established, however, patients and their physicians are reluctant to deintensity therapy.

Dr. Postow’s presentation demonstrated that, with regard to immunotherapy combinations – as in other realms of medical practice – science can lead the way to treatment optimization for individual patients.

We have the potential to reassure patients that treatment de-escalation is a rational and personalized component of treatment optimization through the combination of:

• Identifying new endpoints to quantify treatment benefits and risks.
• SMART trial designs.
• Innovative ways to assess tumor response during each phase of a treatment course.

Precision assessment of immunotherapy effect in individual patients can be a key part of precision medicine.

Dr. Postow disclosed relationships with Aduro, Array BioPharma, Bristol Myers Squibb, Eisai, Incyte, Infinity, Merck, NewLink Genetics, Novartis, and RGenix.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

A simple blood test, claimed to detect more than 50 types of cancer, will be used in a pilot trial by National Health Service England in a bid to increase rates of early-stage diagnosis, in particular for cancers that are currently difficult to diagnose.

“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.

The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”

However, some clinicians have expressed concerns over the potential for false-positive results with the test.

Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.

It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.

The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”

The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.

Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
 

Improving early detection rates

The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.

The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.

A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.

The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.

The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.

“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.

“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.

Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.

“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.

However, some clinicians raised potential concerns.

Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”

Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”

Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”

No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A simple blood test, claimed to detect more than 50 types of cancer, will be used in a pilot trial by National Health Service England in a bid to increase rates of early-stage diagnosis, in particular for cancers that are currently difficult to diagnose.

“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.

The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”

However, some clinicians have expressed concerns over the potential for false-positive results with the test.

Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.

It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.

The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”

The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.

Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
 

Improving early detection rates

The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.

The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.

A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.

The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.

The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.

“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.

“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.

Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.

“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.

However, some clinicians raised potential concerns.

Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”

Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”

Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”

No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A simple blood test, claimed to detect more than 50 types of cancer, will be used in a pilot trial by National Health Service England in a bid to increase rates of early-stage diagnosis, in particular for cancers that are currently difficult to diagnose.

“Early detection, particularly for hard-to-treat conditions like ovarian and pancreatic cancer, has the potential to save many lives,” said NHS Chief Executive Sir Simon Stevens in a statement.

The pilot trial will use the Galleri blood test, developed by Grail. Sir Stevens described the blood test as “promising” and said it could “be a game changer in cancer care, helping thousands more people to get successful treatment.”

However, some clinicians have expressed concerns over the potential for false-positive results with the test.

Results of a study of the Galleri blood test, published earlier this year, showed that the test detected 50 types of cancer with a specificity of 99.3% and a false positive rate of 0.7%.

It also correctly identified the originating tissue in 90% of cases. However, the sensitivity was lower, at 67%, for the 12 most common cancers, as reported at the time.

The senior author of that study, Michael Seiden, MD, PhD, president of the U.S. Oncology Network, The Woodlands, Tex., noted that it was not a screening study: the test had been used in patients with cancer and in healthy volunteers. He said the test “is intended to be complementary to, and not replace, existing guideline-recommended screening tests and might provide new avenues of investigation for cancers that don’t currently have screening tests.”

The Galleri test uses next-generation sequencing to analyze the arrangement of methyl groups on circulating cell-free DNA in a blood sample.

Several other blood tests for cancer are under development, including the CancerSEEK test, which has been reported to be able to identify eight common cancers. It measures circulating tumor DNA from 16 genes and eight protein biomarkers and then uses machine learning to analyze the data.
 

Improving early detection rates

The pilot trial of the blood test is due to start in mid-2021 and will involve 165,000 people.

The trial will include 140,000 individuals aged 50-79 years who were identified through their health records and who have no cancer symptoms. They will undergo blood tests annually for 3 years and will be referred for investigation if a test result is positive.

A second group will include 25,000 people with potential cancer symptoms. These patients will be offered the blood test to speed up their diagnosis after referral to a hospital via the normal channels.

The results of the pilot are expected in 2023. If successful, the test will be rolled out to 1 million individuals from 2024 to 2025.

The pilot trial is part of the NHS Long Term Plan, which aims to increase early detection of cancer. At present, around half of cancers in England are diagnosed in stage I or II; the NHS aims to increase this to 75% by 2028.

“The NHS has set itself an ambitious target,” commented Peter Johnson, MD, PhD, national clinical director for cancer at NHS England and Improvement.

“Tests like this may help us get there far faster, and I am excited to see how this cutting-edge technology will work out as we test it in clinics across the NHS,” he added.

Lord David Prior, chair of NHS England, noted that almost 200,000 people die from cancer in the United Kingdom every year and that “many of these people are diagnosed too late for treatment to be effective.

“This collaboration between the NHS and Grail offers the chance for a wide range of cancers to be diagnosed much earlier and could fundamentally change the outlook for people with cancer,” he said.

However, some clinicians raised potential concerns.

Stephen Duffy, PhD, Center for Cancer Prevention, Queen Mary University of London, described the pilot as “very exciting,” but cautioned: “We will need to find out just how early the test detects cancers and whether it can it be used in a way which minimizes anxiety from false positives.”

Yong-Jie Lu, MD, PhD, also at Queen Mary University of London, said: “It is not clear how early it aims to catch cancer. For a cancer screen test, it needs very high specificity (>99%), otherwise it may end up in a similar situation as the PSA [prostate-specific antigen] test for prostate cancer, or even worse.”

Mangesh Thorat, MD, Cancer Prevention Trials Unit, King’s College London, warned: “It is likely that for every testing round ... there will be about 1,000 false-positive results, and the test may not be able to pinpoint the location of cancer in 3%-4% of those with a true positive result, necessitating a range of imaging and other investigations in these participants.”

No funding for the study has been declared. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Rates of cancer increased by 30% from 1973 to 2015 in adolescents and young adults (AYAs) aged 15–39 years in the United States, according to a review of almost a half million cases in the National Institutes of Health’s Surveillance, Epidemiology, and End Results database.

There was an annual increase of 0.537 new cases per 100,000 people, from 57.2 cases per 100,000 in 1973 to 74.2 in 2015.

Kidney carcinoma led with the highest rate increase. There were also marked increases in thyroid and colorectal carcinoma, germ cell and trophoblastic neoplasms, and melanoma, among others.

The report was published online December 1 in JAMA Network Open.

“Clinicians should be on the lookout for these cancers in their adolescent and young adult patients,” said senior investigator Nicholas Zaorsky, MD, an assistant professor of radiation oncology and public health sciences at the Penn State Cancer Institute, Hershey, Pennsylvania.

“Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed,” he said in a press release.

The reasons for the increases are unclear, but environmental and dietary factors, increasing obesity, and changing screening practices are likely in play, the authors comment. In addition, “cancer screening and overdiagnosis are thought to account for much of the increasing rates of thyroid and kidney carcinoma, among others,” they add.

The American Cancer Society (ACS) recently found similar increases in thyroid, kidney, and colorectal cancer among AYAs, as well as an increase in uterine cancer.

It’s important to note, however, that “this phenomenon is largely driven by trends for thyroid cancer, which is thought to be a result of overdiagnosis,” said ACS surveillance researcher Kimberly Miller, MPH, when asked to comment on the new study.

“As such, it is extremely important to also consider trends in cancer mortality rates among this age group, which are declining overall but are increasing for colorectal and uterine cancers. The fact that both incidence and mortality rates are increasing for these two cancers suggests a true increase in disease burden and certainly requires further attention and research,” she said.

Historically, management of cancer in AYAs has fallen somewhere between pediatric and adult oncology, neither of which capture the distinct biological, social, and economic needs of AYAs. Research has also focused on childhood and adult cancers, leaving cancer in AYAs inadequately studied.

The new findings are “valuable to guide more targeted research and interventions specifically to AYAs,” Zaorsky and colleagues say in their report.

Among female patients ― 59.1% of the study population ― incidence increased for 15 cancers, including kidney carcinoma (annual percent change [APC], 3.632), thyroid carcinoma (APC, 3.456), and myeloma, mast cell, and miscellaneous lymphoreticular neoplasms not otherwise specified (APC, 2.805). Rates of five cancers declined, led by astrocytoma not otherwise specified (APC, –3.369) and carcinoma of the gonads (APC, –1.743).

Among male patients, incidence increased for 14 cancers, including kidney carcinoma (APC, 3.572), unspecified soft tissue sarcoma (APC 2.543), and thyroid carcinoma (APC, 2.273). Incidence fell for seven, led by astrocytoma not otherwise specified (APC, –3.759) and carcinoma of the trachea, bronchus, and lung (APC, –2.635).

Increased testicular cancer rates (APC, 1.246) could be related to greater prenatal exposure to estrogen and progesterone or through dairy consumption; increasing survival of premature infants; and greater exposure to cannabis, among other possibilities, the investigators say.

Increases in colorectal cancer might be related to fewer vegetables and more fat and processed meat in the diet; lack of exercise; and increasing obesity. Human papillomavirus infection has also been implicated.

Higher rates of melanoma could be related to tanning bed use.

Declines in some cancers could be related to greater use of oral contraceptives; laws reducing exposure to benzene and other chemicals; and fewer people smoking.

Although kidney carcinoma has increased at the greatest rate, it’s uncommon. Colorectal and thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads contribute more to the overall increase in cancers among AYAs, the investigators note.

Almost 80% of the patients were White; 10.3% were Black.

The study was funded by the National Center for Advancing Translational Sciences. The investigators have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.