Sharon Worcester

Alcohol is a major preventable risk factor for cancer. New data suggest that reducing alcohol intake reduces the risk of developing an alcohol-related cancer.

The findings, from a large population-based study conducted in Korea, underscore the importance of encouraging individuals to quit drinking or to reduce alcohol consumption to help reduce cancer risk, the authors noted.

The study was published online in JAMA Network Open.

It provides evidence “suggesting that cancer risk can be meaningfully altered by changing the amount of alcoholic beverages consumed,” wrote the authors of an accompanying editorial, Neal D. Freedman, PhD, and Christian C. Abnet, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

“Alcohol consumption is an important cancer risk factor,” they wrote, adding that a “well examined dose-response association has been reported, with highest risks observed among people who drink 3 alcoholic beverages per day and higher.”

The new study shows that a “reduction in use was associated with lower risk, particularly among participants who started drinking at a heavy level,” they noted.

Previous studies have estimated that alcohol use accounts for nearly 4% of newly diagnosed cancers worldwide and nearly 5% of U.S. cancer cases overall.

But the figures are much higher for some specific cancers. That same U.S. study found that alcohol accounts for at least 45% of oral cavity/pharyngeal cancers and at least 25% of laryngeal cancers, as well as 12.1% of female breast cancers, 11.1% of colorectal cancers, 10.5% of liver cancers, and 7.7% of esophageal cancers, as previously reported by this news organization.
 

New findings on reducing intake

This latest study involved an analysis of data on 4.5 million individuals who were adult beneficiaries of the Korean National Health Insurance Service. The median age of the participants was 53.6 years, and they underwent a national health screening in 2009 and 2011.

During median follow-up of 6.4 years, the cancer incidence rate was 7.7 per 1,000 person-years.

Information on alcohol consumption was collected from self-administered questionnaires completed during the health screenings. Participants were categorized on the basis of alcohol consumption: none (0 g/d), mild ( less than 15 g/d), moderate (15-29.9 g/d), and heavy (30 or more g/d).

Compared with those who sustained their alcohol consumption level during the study period, those who increased their level were at higher risk of alcohol-related cancers and all cancers, the investigators found.

The increase in alcohol-related cancer incidence was dose dependent: Those who changed from nondrinking to mild, moderate, or heavy drinking were at increasingly higher risk for alcohol-related cancer, compared with those who remained nondrinkers (adjusted hazard ratios [aHRs], 1.03, 1.10, and 1.34, respectively).

Participants who were mild drinkers at baseline and who quit drinking were at lower risk of alcohol-related cancer, compared with those whose drinking level was sustained (aHR, 0.96). Those with moderate or heavy drinking levels who quit drinking were at higher overall cancer risk than were those who sustained their drinking levels. However, this difference was negated when quitting was sustained, the authors noted.

For heavy drinkers who reduced their drinking levels, cancer incidence was reduced, compared with those who sustained heavy drinking levels. This was true for those who changed from heavy to moderate drinking (aHR, 0.91 for alcohol-related cancers; 0.96 for alcohol-related cancers) and those who changed from heavy to mild drinking (aHR, 0.92 for alcohol-related cancers and all cancers).

“Alcohol cessation and reduction should be reinforced for the prevention of cancer,” concluded the authors.
 

Implications and future directions

The editorialists noted that the study is limited by several factors, such as a short interval between assessments and relatively short follow-up. There is also no information on participants’ alcohol consumption earlier in life or about other healthy lifestyle changes during the study period. In addition, there is no mention of a genetic variant affecting aldehyde dehydrogenase that leads to alcohol-induced flushing, which is common among East Asians.

Despite of these limitations, the study provides “important new findings about the potential role of changes in alcohol consumption in cancer risk,” Dr. Freedman and Dr. Abnet noted. Future studies should examine the association between alcohol intake and cancer risk in other populations and use longer intervals between assessments, they suggested.

“Such studies are needed to move the field forward and inform public health guidance on cancer prevention,” the editorialists concluded.

The authors of the study and the editorialists have disclosed no relevant financial relationships.

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

Alcohol is a major preventable risk factor for cancer. New data suggest that reducing alcohol intake reduces the risk of developing an alcohol-related cancer.

The findings, from a large population-based study conducted in Korea, underscore the importance of encouraging individuals to quit drinking or to reduce alcohol consumption to help reduce cancer risk, the authors noted.

The study was published online in JAMA Network Open.

It provides evidence “suggesting that cancer risk can be meaningfully altered by changing the amount of alcoholic beverages consumed,” wrote the authors of an accompanying editorial, Neal D. Freedman, PhD, and Christian C. Abnet, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

“Alcohol consumption is an important cancer risk factor,” they wrote, adding that a “well examined dose-response association has been reported, with highest risks observed among people who drink 3 alcoholic beverages per day and higher.”

The new study shows that a “reduction in use was associated with lower risk, particularly among participants who started drinking at a heavy level,” they noted.

Previous studies have estimated that alcohol use accounts for nearly 4% of newly diagnosed cancers worldwide and nearly 5% of U.S. cancer cases overall.

But the figures are much higher for some specific cancers. That same U.S. study found that alcohol accounts for at least 45% of oral cavity/pharyngeal cancers and at least 25% of laryngeal cancers, as well as 12.1% of female breast cancers, 11.1% of colorectal cancers, 10.5% of liver cancers, and 7.7% of esophageal cancers, as previously reported by this news organization.
 

New findings on reducing intake

This latest study involved an analysis of data on 4.5 million individuals who were adult beneficiaries of the Korean National Health Insurance Service. The median age of the participants was 53.6 years, and they underwent a national health screening in 2009 and 2011.

During median follow-up of 6.4 years, the cancer incidence rate was 7.7 per 1,000 person-years.

Information on alcohol consumption was collected from self-administered questionnaires completed during the health screenings. Participants were categorized on the basis of alcohol consumption: none (0 g/d), mild ( less than 15 g/d), moderate (15-29.9 g/d), and heavy (30 or more g/d).

Compared with those who sustained their alcohol consumption level during the study period, those who increased their level were at higher risk of alcohol-related cancers and all cancers, the investigators found.

The increase in alcohol-related cancer incidence was dose dependent: Those who changed from nondrinking to mild, moderate, or heavy drinking were at increasingly higher risk for alcohol-related cancer, compared with those who remained nondrinkers (adjusted hazard ratios [aHRs], 1.03, 1.10, and 1.34, respectively).

Participants who were mild drinkers at baseline and who quit drinking were at lower risk of alcohol-related cancer, compared with those whose drinking level was sustained (aHR, 0.96). Those with moderate or heavy drinking levels who quit drinking were at higher overall cancer risk than were those who sustained their drinking levels. However, this difference was negated when quitting was sustained, the authors noted.

For heavy drinkers who reduced their drinking levels, cancer incidence was reduced, compared with those who sustained heavy drinking levels. This was true for those who changed from heavy to moderate drinking (aHR, 0.91 for alcohol-related cancers; 0.96 for alcohol-related cancers) and those who changed from heavy to mild drinking (aHR, 0.92 for alcohol-related cancers and all cancers).

“Alcohol cessation and reduction should be reinforced for the prevention of cancer,” concluded the authors.
 

Implications and future directions

The editorialists noted that the study is limited by several factors, such as a short interval between assessments and relatively short follow-up. There is also no information on participants’ alcohol consumption earlier in life or about other healthy lifestyle changes during the study period. In addition, there is no mention of a genetic variant affecting aldehyde dehydrogenase that leads to alcohol-induced flushing, which is common among East Asians.

Despite of these limitations, the study provides “important new findings about the potential role of changes in alcohol consumption in cancer risk,” Dr. Freedman and Dr. Abnet noted. Future studies should examine the association between alcohol intake and cancer risk in other populations and use longer intervals between assessments, they suggested.

“Such studies are needed to move the field forward and inform public health guidance on cancer prevention,” the editorialists concluded.

The authors of the study and the editorialists have disclosed no relevant financial relationships.

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

Alcohol is a major preventable risk factor for cancer. New data suggest that reducing alcohol intake reduces the risk of developing an alcohol-related cancer.

The findings, from a large population-based study conducted in Korea, underscore the importance of encouraging individuals to quit drinking or to reduce alcohol consumption to help reduce cancer risk, the authors noted.

The study was published online in JAMA Network Open.

It provides evidence “suggesting that cancer risk can be meaningfully altered by changing the amount of alcoholic beverages consumed,” wrote the authors of an accompanying editorial, Neal D. Freedman, PhD, and Christian C. Abnet, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Md.

“Alcohol consumption is an important cancer risk factor,” they wrote, adding that a “well examined dose-response association has been reported, with highest risks observed among people who drink 3 alcoholic beverages per day and higher.”

The new study shows that a “reduction in use was associated with lower risk, particularly among participants who started drinking at a heavy level,” they noted.

Previous studies have estimated that alcohol use accounts for nearly 4% of newly diagnosed cancers worldwide and nearly 5% of U.S. cancer cases overall.

But the figures are much higher for some specific cancers. That same U.S. study found that alcohol accounts for at least 45% of oral cavity/pharyngeal cancers and at least 25% of laryngeal cancers, as well as 12.1% of female breast cancers, 11.1% of colorectal cancers, 10.5% of liver cancers, and 7.7% of esophageal cancers, as previously reported by this news organization.
 

New findings on reducing intake

This latest study involved an analysis of data on 4.5 million individuals who were adult beneficiaries of the Korean National Health Insurance Service. The median age of the participants was 53.6 years, and they underwent a national health screening in 2009 and 2011.

During median follow-up of 6.4 years, the cancer incidence rate was 7.7 per 1,000 person-years.

Information on alcohol consumption was collected from self-administered questionnaires completed during the health screenings. Participants were categorized on the basis of alcohol consumption: none (0 g/d), mild ( less than 15 g/d), moderate (15-29.9 g/d), and heavy (30 or more g/d).

Compared with those who sustained their alcohol consumption level during the study period, those who increased their level were at higher risk of alcohol-related cancers and all cancers, the investigators found.

The increase in alcohol-related cancer incidence was dose dependent: Those who changed from nondrinking to mild, moderate, or heavy drinking were at increasingly higher risk for alcohol-related cancer, compared with those who remained nondrinkers (adjusted hazard ratios [aHRs], 1.03, 1.10, and 1.34, respectively).

Participants who were mild drinkers at baseline and who quit drinking were at lower risk of alcohol-related cancer, compared with those whose drinking level was sustained (aHR, 0.96). Those with moderate or heavy drinking levels who quit drinking were at higher overall cancer risk than were those who sustained their drinking levels. However, this difference was negated when quitting was sustained, the authors noted.

For heavy drinkers who reduced their drinking levels, cancer incidence was reduced, compared with those who sustained heavy drinking levels. This was true for those who changed from heavy to moderate drinking (aHR, 0.91 for alcohol-related cancers; 0.96 for alcohol-related cancers) and those who changed from heavy to mild drinking (aHR, 0.92 for alcohol-related cancers and all cancers).

“Alcohol cessation and reduction should be reinforced for the prevention of cancer,” concluded the authors.
 

Implications and future directions

The editorialists noted that the study is limited by several factors, such as a short interval between assessments and relatively short follow-up. There is also no information on participants’ alcohol consumption earlier in life or about other healthy lifestyle changes during the study period. In addition, there is no mention of a genetic variant affecting aldehyde dehydrogenase that leads to alcohol-induced flushing, which is common among East Asians.

Despite of these limitations, the study provides “important new findings about the potential role of changes in alcohol consumption in cancer risk,” Dr. Freedman and Dr. Abnet noted. Future studies should examine the association between alcohol intake and cancer risk in other populations and use longer intervals between assessments, they suggested.

“Such studies are needed to move the field forward and inform public health guidance on cancer prevention,” the editorialists concluded.

The authors of the study and the editorialists have disclosed no relevant financial relationships.

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

The Food and Drug Administration issued a warning June 30 that the cancer drug duvelisib (Copiktra, Verastem Inc.), a PI3 kinase inhibitor, may increase the risk of death and serious side effects.

Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.

However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.

“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.

More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).

Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.

Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.

A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.

This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”

As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.

“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.

The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.

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

The Food and Drug Administration issued a warning June 30 that the cancer drug duvelisib (Copiktra, Verastem Inc.), a PI3 kinase inhibitor, may increase the risk of death and serious side effects.

Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.

However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.

“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.

More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).

Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.

Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.

A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.

This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”

As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.

“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.

The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.

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

The Food and Drug Administration issued a warning June 30 that the cancer drug duvelisib (Copiktra, Verastem Inc.), a PI3 kinase inhibitor, may increase the risk of death and serious side effects.

Duvelisib was approved in 2018 to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had received at least two prior therapies that did not work or stopped working.

However, more recent 5-year overall survival results from the randomized phase 3 DUO clinical trial found a possible increased risk of death with duvelisib compared with another drug used to treat leukemia and lymphoma, according to an FDA Drug Safety Communication.

“The trial also found Copiktra was associated with a higher risk of serious side effects, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood,” states the warning, which advises prescribers to weigh the risks and benefits of continued use versus use of other treatments.

More specifically, median 5-year overall survival among 319 patients with CLL or SLL in the DUO trial was 52.3 months with duvelisib versus 63.3 months with the monoclonal antibody ofatumumab (hazard ratio, 1.09 overall and 1.06 among patients who received at least two prior lines of therapy).

Serious adverse events of grade 3 or higher were also more common in those treated with duvelisib.

Of note, in April, the FDA also announced it was withdrawing approval of the relapsed or refractory follicular lymphoma indication for duvelisib, following a voluntary request by the drug manufacturer, Secura Bio Inc.

A public meeting will be scheduled to discuss the findings of the trial and whether the drug should continue to be prescribed.

This FDA warning follows the agency’s June 1 withdrawal of approval for umbralisib (Ukoniq), another PI3 kinase inhibitor, following an investigation into a “possible increased risk of death.”

As reported by Medscape, umbralisib had received accelerated approval in February 2021 to treat adults with relapsed or refractory marginal zone lymphoma following at least one prior therapy and those with relapsed or refractory follicular lymphoma who had received at least three prior therapies.

“These safety findings were similar for other medicines in the same PI3 kinase inhibitor class, which were discussed at an advisory committee meeting of non-FDA experts in April 2022,” according to the FDA warning.

The FDA urges patients and health care professionals to report side effects involving duvelisib or other medicines to the FDA MedWatch program.

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

Lisocabtagene maraleucel, also known as liso-cel (Breyanzi), has been approved by the Food and Drug Administration for the second-line treatment of adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL).

This expanded indication is based on findings from the pivotal phase 3 TRANSFORM study, which showed significant and clinically meaningful improvements with CD19-directed chimeric antigen receptor T-cell immunotherapy over salvage chemotherapy followed by high-dose chemotherapy plus autologous stem cell transplant. The latter course of treatment had been the standard of care for more than 2 decades.

Data from the global, randomized, multicenter TRANSFORM study, as reported in December 2021 at the annual meeting of the American Society of Hematology, showed that second-line treatment with liso-cel in 92 patients with r/r LBCL within 12 months after first-line therapy, compared with 92 patient who received standard of care therapy, was associated with highly statistically significant and clinically meaningful improvement in event-free survival (10.1 vs. 2.3 months; hazard ratio, 0.349), complete response rate (66% vs. 39%), and progression-free survival (14.8 vs. 5.7 months; HR, 0.406).

A positive trend in overall survival was also observed (HR, 0.509 at median follow-up of 6.2 months). No new liso-cel safety signals were detected in the second-line setting.

Liso-cel was initially approved in February 2021 for the treatment of adults with LBCL, including diffuse LBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

• Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
• Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant because of comorbidities or age.

Liso-cel is not indicated for the treatment of patients with primary central nervous system lymphoma.

In February 2022, the FDA granted Priority Review status for a Bristol-Myers Squibb supplemental Biologics License Application (sBLA), based on the TRANSFORM study data, to expand the indication to include use after the failure of first-line therapy.

The agent “now has the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care,” Anne Kerber, the BMS senior vice president of cell therapy development, said in a press release at that time.

The European Medicines Agency has also validated a type II variation application for extension of the indication for liso-cel in this setting. Validation of the application “confirms the submission is complete and begins the EMA’s centralized review procedure,” BMS announced in a June 20, 2022, press release.

Liso-cel, which has been available only through a restricted program under a Risk Evaluation and Mitigation Strategy, includes a boxed warning regarding the risk for cytokine release syndrome (CRS) and neurologic toxicities.

The warning states that liso-cel should not be administered to patients with active infection or inflammatory disorders, and that severe or life-threatening CRS should be treated with tocilizumab with or without corticosteroids.

Patients should also be monitored for neurologic events after treatment with liso-cel, and supportive care and/or corticosteroids should be administered as needed.

Lisocabtagene maraleucel, also known as liso-cel (Breyanzi), has been approved by the Food and Drug Administration for the second-line treatment of adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL).

This expanded indication is based on findings from the pivotal phase 3 TRANSFORM study, which showed significant and clinically meaningful improvements with CD19-directed chimeric antigen receptor T-cell immunotherapy over salvage chemotherapy followed by high-dose chemotherapy plus autologous stem cell transplant. The latter course of treatment had been the standard of care for more than 2 decades.

Data from the global, randomized, multicenter TRANSFORM study, as reported in December 2021 at the annual meeting of the American Society of Hematology, showed that second-line treatment with liso-cel in 92 patients with r/r LBCL within 12 months after first-line therapy, compared with 92 patient who received standard of care therapy, was associated with highly statistically significant and clinically meaningful improvement in event-free survival (10.1 vs. 2.3 months; hazard ratio, 0.349), complete response rate (66% vs. 39%), and progression-free survival (14.8 vs. 5.7 months; HR, 0.406).

A positive trend in overall survival was also observed (HR, 0.509 at median follow-up of 6.2 months). No new liso-cel safety signals were detected in the second-line setting.

Liso-cel was initially approved in February 2021 for the treatment of adults with LBCL, including diffuse LBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

• Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
• Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant because of comorbidities or age.

Liso-cel is not indicated for the treatment of patients with primary central nervous system lymphoma.

In February 2022, the FDA granted Priority Review status for a Bristol-Myers Squibb supplemental Biologics License Application (sBLA), based on the TRANSFORM study data, to expand the indication to include use after the failure of first-line therapy.

The agent “now has the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care,” Anne Kerber, the BMS senior vice president of cell therapy development, said in a press release at that time.

The European Medicines Agency has also validated a type II variation application for extension of the indication for liso-cel in this setting. Validation of the application “confirms the submission is complete and begins the EMA’s centralized review procedure,” BMS announced in a June 20, 2022, press release.

Liso-cel, which has been available only through a restricted program under a Risk Evaluation and Mitigation Strategy, includes a boxed warning regarding the risk for cytokine release syndrome (CRS) and neurologic toxicities.

The warning states that liso-cel should not be administered to patients with active infection or inflammatory disorders, and that severe or life-threatening CRS should be treated with tocilizumab with or without corticosteroids.

Patients should also be monitored for neurologic events after treatment with liso-cel, and supportive care and/or corticosteroids should be administered as needed.

Lisocabtagene maraleucel, also known as liso-cel (Breyanzi), has been approved by the Food and Drug Administration for the second-line treatment of adult patients with relapsed or refractory large B-cell lymphoma (r/r LBCL).

This expanded indication is based on findings from the pivotal phase 3 TRANSFORM study, which showed significant and clinically meaningful improvements with CD19-directed chimeric antigen receptor T-cell immunotherapy over salvage chemotherapy followed by high-dose chemotherapy plus autologous stem cell transplant. The latter course of treatment had been the standard of care for more than 2 decades.

Data from the global, randomized, multicenter TRANSFORM study, as reported in December 2021 at the annual meeting of the American Society of Hematology, showed that second-line treatment with liso-cel in 92 patients with r/r LBCL within 12 months after first-line therapy, compared with 92 patient who received standard of care therapy, was associated with highly statistically significant and clinically meaningful improvement in event-free survival (10.1 vs. 2.3 months; hazard ratio, 0.349), complete response rate (66% vs. 39%), and progression-free survival (14.8 vs. 5.7 months; HR, 0.406).

A positive trend in overall survival was also observed (HR, 0.509 at median follow-up of 6.2 months). No new liso-cel safety signals were detected in the second-line setting.

Liso-cel was initially approved in February 2021 for the treatment of adults with LBCL, including diffuse LBCL not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have:

• Refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy.
• Refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant because of comorbidities or age.

Liso-cel is not indicated for the treatment of patients with primary central nervous system lymphoma.

In February 2022, the FDA granted Priority Review status for a Bristol-Myers Squibb supplemental Biologics License Application (sBLA), based on the TRANSFORM study data, to expand the indication to include use after the failure of first-line therapy.

The agent “now has the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care,” Anne Kerber, the BMS senior vice president of cell therapy development, said in a press release at that time.

The European Medicines Agency has also validated a type II variation application for extension of the indication for liso-cel in this setting. Validation of the application “confirms the submission is complete and begins the EMA’s centralized review procedure,” BMS announced in a June 20, 2022, press release.

Liso-cel, which has been available only through a restricted program under a Risk Evaluation and Mitigation Strategy, includes a boxed warning regarding the risk for cytokine release syndrome (CRS) and neurologic toxicities.

The warning states that liso-cel should not be administered to patients with active infection or inflammatory disorders, and that severe or life-threatening CRS should be treated with tocilizumab with or without corticosteroids.

Patients should also be monitored for neurologic events after treatment with liso-cel, and supportive care and/or corticosteroids should be administered as needed.

CHICAGO -- High-dose ifosfamide has shown superior survival benefit over three other chemotherapy regimens for patients with recurring or refractory primary Ewing sarcoma (RR-ES) in the practice-changing rEECur trial.

This international trial is the first randomized head-to-head comparison of commonly used chemotherapy regimens in patients with the rare and deadly disease.

The study results are expected to change the standard of care and be practice-changing on a global scale, commented Julie Gralow, MD, chief medical officer at the annual meeting of the American Society of Clinical Oncology, where the results were presented June 5 during a plenary session.

Ewing sarcoma is a very rare cancer of the bone and soft tissue that mainly affects children and young adults, particularly in the second decade of life, explained lead author Martin McCabe, MD, clinical senior lecturer in pediatric, teenage, and young adult cancer at the University of Manchester (England). The incidence rate is 3.2 per million people under age 25 years, he said.

Dr. Gralow explained in an interview that treatment of Ewing sarcoma differs from one cancer center to another. Several different chemotherapy regimens are being used, all based on single-arm trials, with no consensus on which is best.

This international trial set out to answer that question and compared four different regimens. Participating centers were “able to solve a question by partnering, coming together, and even in a very rare population get enough patients to define the winner,” she said.

Earlier findings from this trial had shown that ifosfamide had improved survival, compared with gemcitabine and docetaxel and compared with irinotecan and temozolomide.

At the meeting, results of the comparison of ifosfamide versus a combination of topotecan and cyclophosphamide (TC) were presented.

Median overall survival was 15.4 versus 10.5 months with ifosfamide versus TC, and 1-year overall survival was 55% versus 45%, respectively, for a 94% probability that ifosfamide is better than TC for overall survival, Dr. McCabe reported.  

Median event-free survival was 16.8 months in 73 patients in the ifosfamide group versus 10.4 months for 73 patients in the TC group. Six-month event-free survival was 47% versus 37%, respectively. “Given the observed data, there is a 96% probability that ifosfamide is better than TC for event-free survival,” he said.   

High-dose ifosfamide prolonged median event-free survival by 5.7 months, compared with 3.7 months for TC.

Notably, greater event-free survival and overall survival differences were observed for patients under age 14 years, compared with those aged 14 and older, Dr. McCabe noted.

As for toxicity, similar rates of neutropenic infections were seen in the two groups, but more severe renal and brain toxicity were observed with ifosfamide, with both occurring in less than 10% of patients, he said.

Despite the practice-changing results, Dr. McCabe stressed that the “differences [between treatments] are quite small, and what we actually need is better drugs to cure more patients.”

The rEEcur trial is continuing to recruit patients to the ifosfamide group, and a fifth chemotherapy group of carboplatin and etoposide has been added.

Later this year, investigators also plan to add a new group with a molecular targeted therapeutic.
 

Important global collaboration

Dr. Gralow emphasized the global collaboration that was behind this trial, which set out to answer important questions about how best to treat a rare disease. “In this really terrific collaboration ... there was an agreement to test all these regimens that are commonly used, and so we now have data on efficacy and toxicity.”

“It’s a really important concept in rare diseases: If we all work together, we actually can study them and get answers,” she said.

“I think pediatricians and oncologists are [now] better able to talk about the risks and benefits [of the regimens],” she added.

Vicki L. Keedy, MD, an ASCO Expert in sarcoma, concurred. The findings from the rEECur trial “could help physicians talk with patients and their families about the likelihood of response, survival, and toxicity for each regimen available for relapsed Ewing sarcoma based on objective, randomized data,” she commented in an ASCO press release. 

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

CHICAGO -- High-dose ifosfamide has shown superior survival benefit over three other chemotherapy regimens for patients with recurring or refractory primary Ewing sarcoma (RR-ES) in the practice-changing rEECur trial.

This international trial is the first randomized head-to-head comparison of commonly used chemotherapy regimens in patients with the rare and deadly disease.

The study results are expected to change the standard of care and be practice-changing on a global scale, commented Julie Gralow, MD, chief medical officer at the annual meeting of the American Society of Clinical Oncology, where the results were presented June 5 during a plenary session.

Ewing sarcoma is a very rare cancer of the bone and soft tissue that mainly affects children and young adults, particularly in the second decade of life, explained lead author Martin McCabe, MD, clinical senior lecturer in pediatric, teenage, and young adult cancer at the University of Manchester (England). The incidence rate is 3.2 per million people under age 25 years, he said.

Dr. Gralow explained in an interview that treatment of Ewing sarcoma differs from one cancer center to another. Several different chemotherapy regimens are being used, all based on single-arm trials, with no consensus on which is best.

This international trial set out to answer that question and compared four different regimens. Participating centers were “able to solve a question by partnering, coming together, and even in a very rare population get enough patients to define the winner,” she said.

Earlier findings from this trial had shown that ifosfamide had improved survival, compared with gemcitabine and docetaxel and compared with irinotecan and temozolomide.

At the meeting, results of the comparison of ifosfamide versus a combination of topotecan and cyclophosphamide (TC) were presented.

Median overall survival was 15.4 versus 10.5 months with ifosfamide versus TC, and 1-year overall survival was 55% versus 45%, respectively, for a 94% probability that ifosfamide is better than TC for overall survival, Dr. McCabe reported.  

Median event-free survival was 16.8 months in 73 patients in the ifosfamide group versus 10.4 months for 73 patients in the TC group. Six-month event-free survival was 47% versus 37%, respectively. “Given the observed data, there is a 96% probability that ifosfamide is better than TC for event-free survival,” he said.   

High-dose ifosfamide prolonged median event-free survival by 5.7 months, compared with 3.7 months for TC.

Notably, greater event-free survival and overall survival differences were observed for patients under age 14 years, compared with those aged 14 and older, Dr. McCabe noted.

As for toxicity, similar rates of neutropenic infections were seen in the two groups, but more severe renal and brain toxicity were observed with ifosfamide, with both occurring in less than 10% of patients, he said.

Despite the practice-changing results, Dr. McCabe stressed that the “differences [between treatments] are quite small, and what we actually need is better drugs to cure more patients.”

The rEEcur trial is continuing to recruit patients to the ifosfamide group, and a fifth chemotherapy group of carboplatin and etoposide has been added.

Later this year, investigators also plan to add a new group with a molecular targeted therapeutic.
 

Important global collaboration

Dr. Gralow emphasized the global collaboration that was behind this trial, which set out to answer important questions about how best to treat a rare disease. “In this really terrific collaboration ... there was an agreement to test all these regimens that are commonly used, and so we now have data on efficacy and toxicity.”

“It’s a really important concept in rare diseases: If we all work together, we actually can study them and get answers,” she said.

“I think pediatricians and oncologists are [now] better able to talk about the risks and benefits [of the regimens],” she added.

Vicki L. Keedy, MD, an ASCO Expert in sarcoma, concurred. The findings from the rEECur trial “could help physicians talk with patients and their families about the likelihood of response, survival, and toxicity for each regimen available for relapsed Ewing sarcoma based on objective, randomized data,” she commented in an ASCO press release. 

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

CHICAGO -- High-dose ifosfamide has shown superior survival benefit over three other chemotherapy regimens for patients with recurring or refractory primary Ewing sarcoma (RR-ES) in the practice-changing rEECur trial.

This international trial is the first randomized head-to-head comparison of commonly used chemotherapy regimens in patients with the rare and deadly disease.

The study results are expected to change the standard of care and be practice-changing on a global scale, commented Julie Gralow, MD, chief medical officer at the annual meeting of the American Society of Clinical Oncology, where the results were presented June 5 during a plenary session.

Ewing sarcoma is a very rare cancer of the bone and soft tissue that mainly affects children and young adults, particularly in the second decade of life, explained lead author Martin McCabe, MD, clinical senior lecturer in pediatric, teenage, and young adult cancer at the University of Manchester (England). The incidence rate is 3.2 per million people under age 25 years, he said.

Dr. Gralow explained in an interview that treatment of Ewing sarcoma differs from one cancer center to another. Several different chemotherapy regimens are being used, all based on single-arm trials, with no consensus on which is best.

This international trial set out to answer that question and compared four different regimens. Participating centers were “able to solve a question by partnering, coming together, and even in a very rare population get enough patients to define the winner,” she said.

Earlier findings from this trial had shown that ifosfamide had improved survival, compared with gemcitabine and docetaxel and compared with irinotecan and temozolomide.

At the meeting, results of the comparison of ifosfamide versus a combination of topotecan and cyclophosphamide (TC) were presented.

Median overall survival was 15.4 versus 10.5 months with ifosfamide versus TC, and 1-year overall survival was 55% versus 45%, respectively, for a 94% probability that ifosfamide is better than TC for overall survival, Dr. McCabe reported.  

Median event-free survival was 16.8 months in 73 patients in the ifosfamide group versus 10.4 months for 73 patients in the TC group. Six-month event-free survival was 47% versus 37%, respectively. “Given the observed data, there is a 96% probability that ifosfamide is better than TC for event-free survival,” he said.   

High-dose ifosfamide prolonged median event-free survival by 5.7 months, compared with 3.7 months for TC.

Notably, greater event-free survival and overall survival differences were observed for patients under age 14 years, compared with those aged 14 and older, Dr. McCabe noted.

As for toxicity, similar rates of neutropenic infections were seen in the two groups, but more severe renal and brain toxicity were observed with ifosfamide, with both occurring in less than 10% of patients, he said.

Despite the practice-changing results, Dr. McCabe stressed that the “differences [between treatments] are quite small, and what we actually need is better drugs to cure more patients.”

The rEEcur trial is continuing to recruit patients to the ifosfamide group, and a fifth chemotherapy group of carboplatin and etoposide has been added.

Later this year, investigators also plan to add a new group with a molecular targeted therapeutic.
 

Important global collaboration

Dr. Gralow emphasized the global collaboration that was behind this trial, which set out to answer important questions about how best to treat a rare disease. “In this really terrific collaboration ... there was an agreement to test all these regimens that are commonly used, and so we now have data on efficacy and toxicity.”

“It’s a really important concept in rare diseases: If we all work together, we actually can study them and get answers,” she said.

“I think pediatricians and oncologists are [now] better able to talk about the risks and benefits [of the regimens],” she added.

Vicki L. Keedy, MD, an ASCO Expert in sarcoma, concurred. The findings from the rEECur trial “could help physicians talk with patients and their families about the likelihood of response, survival, and toxicity for each regimen available for relapsed Ewing sarcoma based on objective, randomized data,” she commented in an ASCO press release. 

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

CHICAGO – The COVID pandemic pushed telemedicine forward as a safe, accessible, and more widely reimbursed approach to care delivery for patients with cancer, but uptake of telemedicine was plagued by inequities, a retrospective study suggests.

Before March 2020, only a very small percentage of patients with cancer used telemedicine services.

By November 2021, nearly 16% of patients initiating cancer treatment were using this approach.

However, certain groups were less likely to use telemedicine, in particular, patients who were Black, uninsured, did not live in cities, and were less affluent, noted lead author Jenny S. Guadamuz, PhD, a quantitative scientist at Flatiron Health and a postdoctoral research associate at the University of Southern California, Los Angeles.

The results are concerning because they suggest that telemedicine expansion could widen cancer care disparities, Dr. Guadamuz said. Previous studies found racial disparities in care access and outcomes early on in the pandemic.

“These findings are critically important considering recent efforts to make coverage of telemedicine services permanent, instead of tied to the [Health and Human Services] public health emergency declaration,” she said. “There are also efforts to increase reimbursement rates for telemedicine services by Medicare, several Medicaid programs, and private insurers.”

This study was highlighted at a press briefing held in advance of the American Society of Clinical Oncology annual meeting, where it will be presented at a poster session (abstract 6511).

ASCO President Everett E. Vokes, MD, said telemedicine is “an important tool to communicate with patients” but that it is important to consider the “digital divide.”

He also emphasized the need “to expand and learn to use telehealth not in a crisis but as part of our regular care moving forward.” In July 2021, as telemedicine services were expanding, ASCO released practice recommendations specific to telehealth and oncology.

“Telemedicine can improve access to timely cancer care, but, as this study points out, telemedicine must be available equitably, so that every patient can access the care they need and deserve,” he said in a press statement.
 

Study details

For the study, Dr. Guadamuz and colleagues assessed telemedicine uptake by nearly 27,000 patients in a Flatiron electronic health record–derived deidentified database of patients who initiated treatment for any of 21 common cancers at about 280 community oncology clinics between March 2020 and November 2021.

They found that Black patients were significantly less likely than were White patients to use telemedicine (13.2% vs. 15.6%; odds ratio [OR], 0.82), as were patients without documented insurance, compared with those who were well insured (11.6% vs. 16.4%; OR, 0.68).

Those in rural and suburban areas were less likely than were those in urban areas to use telemedicine (9.7% and 13.0% vs. 17.7%; ORs, 0.50 and 0.69, respectively), and those in less affluent vs. more affluent areas were also less likely to use telemedicine (10.6% vs. 23.6%, OR, 0.39).

Dr. Guadamuz noted that the differences remained statistically significant after adjustment for clinical characteristics and that racial inequities were seen across cancer types and over time.

Future work should assess other potential characteristics associated with telemedicine inequities, evaluate whether health care delivered via telemedicine is of similar quality as in-person services, and determine the types of practice that are providing telemedicine more equitably to their patients, she concluded.

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

CHICAGO – The COVID pandemic pushed telemedicine forward as a safe, accessible, and more widely reimbursed approach to care delivery for patients with cancer, but uptake of telemedicine was plagued by inequities, a retrospective study suggests.

Before March 2020, only a very small percentage of patients with cancer used telemedicine services.

By November 2021, nearly 16% of patients initiating cancer treatment were using this approach.

However, certain groups were less likely to use telemedicine, in particular, patients who were Black, uninsured, did not live in cities, and were less affluent, noted lead author Jenny S. Guadamuz, PhD, a quantitative scientist at Flatiron Health and a postdoctoral research associate at the University of Southern California, Los Angeles.

The results are concerning because they suggest that telemedicine expansion could widen cancer care disparities, Dr. Guadamuz said. Previous studies found racial disparities in care access and outcomes early on in the pandemic.

“These findings are critically important considering recent efforts to make coverage of telemedicine services permanent, instead of tied to the [Health and Human Services] public health emergency declaration,” she said. “There are also efforts to increase reimbursement rates for telemedicine services by Medicare, several Medicaid programs, and private insurers.”

This study was highlighted at a press briefing held in advance of the American Society of Clinical Oncology annual meeting, where it will be presented at a poster session (abstract 6511).

ASCO President Everett E. Vokes, MD, said telemedicine is “an important tool to communicate with patients” but that it is important to consider the “digital divide.”

He also emphasized the need “to expand and learn to use telehealth not in a crisis but as part of our regular care moving forward.” In July 2021, as telemedicine services were expanding, ASCO released practice recommendations specific to telehealth and oncology.

“Telemedicine can improve access to timely cancer care, but, as this study points out, telemedicine must be available equitably, so that every patient can access the care they need and deserve,” he said in a press statement.
 

Study details

For the study, Dr. Guadamuz and colleagues assessed telemedicine uptake by nearly 27,000 patients in a Flatiron electronic health record–derived deidentified database of patients who initiated treatment for any of 21 common cancers at about 280 community oncology clinics between March 2020 and November 2021.

They found that Black patients were significantly less likely than were White patients to use telemedicine (13.2% vs. 15.6%; odds ratio [OR], 0.82), as were patients without documented insurance, compared with those who were well insured (11.6% vs. 16.4%; OR, 0.68).

Those in rural and suburban areas were less likely than were those in urban areas to use telemedicine (9.7% and 13.0% vs. 17.7%; ORs, 0.50 and 0.69, respectively), and those in less affluent vs. more affluent areas were also less likely to use telemedicine (10.6% vs. 23.6%, OR, 0.39).

Dr. Guadamuz noted that the differences remained statistically significant after adjustment for clinical characteristics and that racial inequities were seen across cancer types and over time.

Future work should assess other potential characteristics associated with telemedicine inequities, evaluate whether health care delivered via telemedicine is of similar quality as in-person services, and determine the types of practice that are providing telemedicine more equitably to their patients, she concluded.

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

CHICAGO – The COVID pandemic pushed telemedicine forward as a safe, accessible, and more widely reimbursed approach to care delivery for patients with cancer, but uptake of telemedicine was plagued by inequities, a retrospective study suggests.

Before March 2020, only a very small percentage of patients with cancer used telemedicine services.

By November 2021, nearly 16% of patients initiating cancer treatment were using this approach.

However, certain groups were less likely to use telemedicine, in particular, patients who were Black, uninsured, did not live in cities, and were less affluent, noted lead author Jenny S. Guadamuz, PhD, a quantitative scientist at Flatiron Health and a postdoctoral research associate at the University of Southern California, Los Angeles.

The results are concerning because they suggest that telemedicine expansion could widen cancer care disparities, Dr. Guadamuz said. Previous studies found racial disparities in care access and outcomes early on in the pandemic.

“These findings are critically important considering recent efforts to make coverage of telemedicine services permanent, instead of tied to the [Health and Human Services] public health emergency declaration,” she said. “There are also efforts to increase reimbursement rates for telemedicine services by Medicare, several Medicaid programs, and private insurers.”

This study was highlighted at a press briefing held in advance of the American Society of Clinical Oncology annual meeting, where it will be presented at a poster session (abstract 6511).

ASCO President Everett E. Vokes, MD, said telemedicine is “an important tool to communicate with patients” but that it is important to consider the “digital divide.”

He also emphasized the need “to expand and learn to use telehealth not in a crisis but as part of our regular care moving forward.” In July 2021, as telemedicine services were expanding, ASCO released practice recommendations specific to telehealth and oncology.

“Telemedicine can improve access to timely cancer care, but, as this study points out, telemedicine must be available equitably, so that every patient can access the care they need and deserve,” he said in a press statement.
 

Study details

For the study, Dr. Guadamuz and colleagues assessed telemedicine uptake by nearly 27,000 patients in a Flatiron electronic health record–derived deidentified database of patients who initiated treatment for any of 21 common cancers at about 280 community oncology clinics between March 2020 and November 2021.

They found that Black patients were significantly less likely than were White patients to use telemedicine (13.2% vs. 15.6%; odds ratio [OR], 0.82), as were patients without documented insurance, compared with those who were well insured (11.6% vs. 16.4%; OR, 0.68).

Those in rural and suburban areas were less likely than were those in urban areas to use telemedicine (9.7% and 13.0% vs. 17.7%; ORs, 0.50 and 0.69, respectively), and those in less affluent vs. more affluent areas were also less likely to use telemedicine (10.6% vs. 23.6%, OR, 0.39).

Dr. Guadamuz noted that the differences remained statistically significant after adjustment for clinical characteristics and that racial inequities were seen across cancer types and over time.

Future work should assess other potential characteristics associated with telemedicine inequities, evaluate whether health care delivered via telemedicine is of similar quality as in-person services, and determine the types of practice that are providing telemedicine more equitably to their patients, she concluded.

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

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

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

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

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

Learning that a family member has cancer can be devastating enough. Waiting to find out whether a loved one can afford their treatment takes the concern to another level.

That was the case for health policy expert Stacie B. Dusetzina, PhD, when her mother was diagnosed with metastatic breast cancer.

“There is this period where you are waiting to learn more about the cancer type and treatment options, and, of course, what might be covered by your health plan,” Dr. Dusetzina, an associate professor at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview. “Knowing as much as I do about coverage for prescription drugs in Medicare Part D, I was worried we would be in a situation where my mom had to spend over $15,000 out-of-pocket every year for one of these drugs.”

That $15,000 would have taken a large chunk of her retirement income and could make treatment unaffordable down the line.

This situation is hardly unique.

Many patients with cancer who rely on Medicare Part D face an impossible choice: “Your money or your life,” Dr. Dusetzina said.

In a recent perspective in the New England Journal of Medicine, Dr. Dusetzina detailed how subtle variations in people’s cancer type can have major implications for their out-of-pocket drug costs.

The difference in cost comes down to whether drugs are delivered as pills or infusions. Oral agents are almost always covered under a health plan’s pharmacy benefit (Medicare Part D), while physician-administered drugs are covered under the medical benefit (Medicare Part B).

According to Dr. Dusetzina, Medicare beneficiaries can face substantial, possibly “unlimited,” out-of-pocket costs for drugs covered under Part D if they don’t qualify for low-income subsidies. On the other hand, most beneficiaries receiving physician-administered drugs covered under Part B have supplemental coverage, which reduces or eliminates out-of-pocket costs.

Dr. Dusetzina broke down the expected first fill and yearly out-of-pocket costs associated with 10 oral cancer drugs covered under Part D. These costs ranged from $3,100 to $3,392 for a first fill and $10,592 to $14,067 for one year.

In a candid Twitter thread, Dr. Dusetzina opened up more about the issues highlighted in her piece: “This paper is about #PartD and Cancer. It is also about #pharmacoequity ... This is about how screwed you are if you need cancer treatment and your treatment happens to be covered by #PartD and not #PartB.”

“This is ARBITRARY and INEQUITABLE,” she added.

What’s “arbitrary,” Dr. Dusetzina explains, is that a rather small, chance distinction in cancer type or subtype can be the difference between affording and not affording treatment – and potentially between life and death.

Take the drug costs for two similar patients with breast cancer.

Patient A has hormone receptor–positive, human epidermal growth factor receptor type 2 (HER2)–negative breast cancer and thus would likely receive first-line therapy with two oral agents: an aromatase inhibitor and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor, most often palbociclib (Ibrance).

For palbociclib alone, out-of-pocket costs would come to $3,100 for the first fill and nearly $10,600 over a year for a Part D beneficiary who doesn’t qualify for low-income subsidies.

Now take patient B who has HER2–positive metastatic breast cancer. This person would likely receive first-line treatment with trastuzumab (Herceptin), pertuzumab (Perjeta), and a taxane – a combination covered under Part B, which would be subject to an out-of-pocket cap or covered with limited or no cost sharing.

This difference in cancer subtype leaves some patients “paying substantially more for their cancer treatment than others, despite the same goal of extending or improving their lives,” Dr. Dusetzina writes.

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

Imiquimod cream is a safe, effective, first-line alternative to surgery for the treatment of vulvar high-grade squamous intraepithelial lesions (vHSILs), suggest the results from the first randomized trial to compare the two approaches directly.

The findings provide women with human papillomavirus (HPV)–related precancerous lesions with a new treatment option that can circumvent drawbacks of surgery, according to first author Gerda Trutnovsky, MD, deputy head of the Division of Gynecology at the Medical University of Graz, Austria.

“Surgical removal of [vulvar intraepithelial neoplasia] can cause wound healing disorders, scarring, and even sexual complaints later on,” she explained in a press statement. Further, recurrences are common, and repeat surgeries are often necessary, she said.

The results from the trial show that “imiquimod cream was effective and well tolerated, and the rate of success of this treatment equaled that of surgery,” Dr. Trutnovsky said.

The study was published online in The Lancet.

The findings are of note because HPV vaccination rates remain low, and the incidence of both cervical and vulvar intraepithelial neoplasia has increased in recent years, particularly among younger women, the authors comment.
 

First head-to-head trial

For the trial, Dr. Trutnovsky and her colleagues randomly assigned 110 women with vHSIL to receive either imiquimod treatment or surgery between June 2013 and January 2020. Of these patients, 78% had unifocal lesions, and 22% had multifocal lesions.

The participants (aged 18-90 years) were recruited from six hospitals in Austria. All had histologically confirmed vHSIL with visible unifocal or multifocal lesions. Those with suspected invasive disease, a history of vulvar cancer or severe inflammatory dermatosis of the vulva, or who had undergone active treatment for vHSIL in the prior 3 months were excluded.

Imiquimod treatment was self-administered. The dose was slowly escalated to no more than three times per week for 4-6 months. Surgery involved either excision or ablation.

The team reports that 98 patients (of the 110 who were randomly assigned) completed the study: 46 in the imiquinod arm and 52 in the surgery arm.

Complete clinical response rates at 6 months were 80% with imiquimod versus 79% with surgery. No significant difference was observed between the groups with respect to HPV clearance, adverse events, and treatment satisfaction, the authors report.

“Long-term follow-up ... is ongoing and will assess the effect of treatment modality on recurrence rates,” the team comments.

Dr. Trutnovsky and colleagues recommend that patients with vHSIL be counseled regarding the potential benefits and risks of treatment options. “On the basis of our results, the oncological safety of imiquimod treatment can be assumed as long as regular clinical check-ups are carried out,” they write.

They also note that good patient compliance is important for treatment with imiquimod to be successful and that surgery might remain the treatment of choice for patients who may not be adherent to treatment.

“In all other women with vHSIL, imiquimod can be considered a first-line treatment option,” the authors conclude.

The study was funded by the Austrian Science Fund and Austrian Gynaecological Oncology group. The authors have disclosed no relevant financial relationships.

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

Imiquimod cream is a safe, effective, first-line alternative to surgery for the treatment of vulvar high-grade squamous intraepithelial lesions (vHSILs), suggest the results from the first randomized trial to compare the two approaches directly.

The findings provide women with human papillomavirus (HPV)–related precancerous lesions with a new treatment option that can circumvent drawbacks of surgery, according to first author Gerda Trutnovsky, MD, deputy head of the Division of Gynecology at the Medical University of Graz, Austria.

“Surgical removal of [vulvar intraepithelial neoplasia] can cause wound healing disorders, scarring, and even sexual complaints later on,” she explained in a press statement. Further, recurrences are common, and repeat surgeries are often necessary, she said.

The results from the trial show that “imiquimod cream was effective and well tolerated, and the rate of success of this treatment equaled that of surgery,” Dr. Trutnovsky said.

The study was published online in The Lancet.

The findings are of note because HPV vaccination rates remain low, and the incidence of both cervical and vulvar intraepithelial neoplasia has increased in recent years, particularly among younger women, the authors comment.
 

First head-to-head trial

For the trial, Dr. Trutnovsky and her colleagues randomly assigned 110 women with vHSIL to receive either imiquimod treatment or surgery between June 2013 and January 2020. Of these patients, 78% had unifocal lesions, and 22% had multifocal lesions.

The participants (aged 18-90 years) were recruited from six hospitals in Austria. All had histologically confirmed vHSIL with visible unifocal or multifocal lesions. Those with suspected invasive disease, a history of vulvar cancer or severe inflammatory dermatosis of the vulva, or who had undergone active treatment for vHSIL in the prior 3 months were excluded.

Imiquimod treatment was self-administered. The dose was slowly escalated to no more than three times per week for 4-6 months. Surgery involved either excision or ablation.

The team reports that 98 patients (of the 110 who were randomly assigned) completed the study: 46 in the imiquinod arm and 52 in the surgery arm.

Complete clinical response rates at 6 months were 80% with imiquimod versus 79% with surgery. No significant difference was observed between the groups with respect to HPV clearance, adverse events, and treatment satisfaction, the authors report.

“Long-term follow-up ... is ongoing and will assess the effect of treatment modality on recurrence rates,” the team comments.

Dr. Trutnovsky and colleagues recommend that patients with vHSIL be counseled regarding the potential benefits and risks of treatment options. “On the basis of our results, the oncological safety of imiquimod treatment can be assumed as long as regular clinical check-ups are carried out,” they write.

They also note that good patient compliance is important for treatment with imiquimod to be successful and that surgery might remain the treatment of choice for patients who may not be adherent to treatment.

“In all other women with vHSIL, imiquimod can be considered a first-line treatment option,” the authors conclude.

The study was funded by the Austrian Science Fund and Austrian Gynaecological Oncology group. The authors have disclosed no relevant financial relationships.

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

Imiquimod cream is a safe, effective, first-line alternative to surgery for the treatment of vulvar high-grade squamous intraepithelial lesions (vHSILs), suggest the results from the first randomized trial to compare the two approaches directly.

The findings provide women with human papillomavirus (HPV)–related precancerous lesions with a new treatment option that can circumvent drawbacks of surgery, according to first author Gerda Trutnovsky, MD, deputy head of the Division of Gynecology at the Medical University of Graz, Austria.

“Surgical removal of [vulvar intraepithelial neoplasia] can cause wound healing disorders, scarring, and even sexual complaints later on,” she explained in a press statement. Further, recurrences are common, and repeat surgeries are often necessary, she said.

The results from the trial show that “imiquimod cream was effective and well tolerated, and the rate of success of this treatment equaled that of surgery,” Dr. Trutnovsky said.

The study was published online in The Lancet.

The findings are of note because HPV vaccination rates remain low, and the incidence of both cervical and vulvar intraepithelial neoplasia has increased in recent years, particularly among younger women, the authors comment.
 

First head-to-head trial

For the trial, Dr. Trutnovsky and her colleagues randomly assigned 110 women with vHSIL to receive either imiquimod treatment or surgery between June 2013 and January 2020. Of these patients, 78% had unifocal lesions, and 22% had multifocal lesions.

The participants (aged 18-90 years) were recruited from six hospitals in Austria. All had histologically confirmed vHSIL with visible unifocal or multifocal lesions. Those with suspected invasive disease, a history of vulvar cancer or severe inflammatory dermatosis of the vulva, or who had undergone active treatment for vHSIL in the prior 3 months were excluded.

Imiquimod treatment was self-administered. The dose was slowly escalated to no more than three times per week for 4-6 months. Surgery involved either excision or ablation.

The team reports that 98 patients (of the 110 who were randomly assigned) completed the study: 46 in the imiquinod arm and 52 in the surgery arm.

Complete clinical response rates at 6 months were 80% with imiquimod versus 79% with surgery. No significant difference was observed between the groups with respect to HPV clearance, adverse events, and treatment satisfaction, the authors report.

“Long-term follow-up ... is ongoing and will assess the effect of treatment modality on recurrence rates,” the team comments.

Dr. Trutnovsky and colleagues recommend that patients with vHSIL be counseled regarding the potential benefits and risks of treatment options. “On the basis of our results, the oncological safety of imiquimod treatment can be assumed as long as regular clinical check-ups are carried out,” they write.

They also note that good patient compliance is important for treatment with imiquimod to be successful and that surgery might remain the treatment of choice for patients who may not be adherent to treatment.

“In all other women with vHSIL, imiquimod can be considered a first-line treatment option,” the authors conclude.

The study was funded by the Austrian Science Fund and Austrian Gynaecological Oncology group. The authors have disclosed no relevant financial relationships.

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

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

The preclinical phase of chronic lymphocytic leukemia (CLL) may be exist longer than previously thought, even in adverse-prognostic cases, as suggested by a sequencing analysis of blood samples obtained up to 22 years prior to CLL diagnosis.

Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”

“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.

Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.

Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.

This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.

“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”

Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.

“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.

The investigators also found that:

• Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
• High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
• The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
• No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.

“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.

The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”

The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”

“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.

In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .

They also raise new questions and point to new directions for research, Dr. Marti noted.

“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”

The study authors and Dr. Marti reported having no competing financial interests.

The preclinical phase of chronic lymphocytic leukemia (CLL) may be exist longer than previously thought, even in adverse-prognostic cases, as suggested by a sequencing analysis of blood samples obtained up to 22 years prior to CLL diagnosis.

Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”

“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.

Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.

Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.

This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.

“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”

Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.

“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.

The investigators also found that:

• Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
• High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
• The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
• No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.

“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.

The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”

The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”

“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.

In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .

They also raise new questions and point to new directions for research, Dr. Marti noted.

“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”

The study authors and Dr. Marti reported having no competing financial interests.

The preclinical phase of chronic lymphocytic leukemia (CLL) may be exist longer than previously thought, even in adverse-prognostic cases, as suggested by a sequencing analysis of blood samples obtained up to 22 years prior to CLL diagnosis.

Previous analyses showed that monoclonal B-cell lymphocytosis (MBL), a CLL precursor state, has been detected up to 6 years before CLL diagnosis, the investigators explained, noting that “[a]nother prognostically relevant immunogenetic feature of CLL concerns the stereotype of the B-cell receptor immunoglobulins (BcR IG).”

“Indeed, distinct stereotyped subsets can be defined by the expression of shared sequence motifs and are associated with particular presentation and outcomes,” P. Martijn Kolijn, PhD, a researcher in the department of immunology at Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues wrote in a brief report published online in Blood. In an effort to “gain insight into the composition of the BcR IG repertoire during the early stages of CLL,” the investigators utilized next-generation sequencing to analyze 124 blood samples taken from healthy individuals up to 22 years before they received a diagnosis of CLL or small lymphocytic leukemia (SLL). An additional 118 matched control samples were also analyzed.

Study subjects were participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

“First, unsurprisingly, we observed a significant difference in the frequency of the dominant clonotype in CLL patients versus controls with a median frequency of 54.9%, compared to only 0.38% in controls,” they wrote.

Among 28 patients whose lymphocyte counts were measured at baseline, 10 showed evidence of lymphocytosis up to 8 years before CLL diagnosis.

This suggests undiagnosed instances of high-count MBL (cases with a cell count above 0.5x 109 cells/L, which can progress to CLL) or asymptomatic CLL, they explained.

“In contrast, next-generation sequencing results showed detectable skewing of the IGH gene repertoire in 21/28 patients up to 15 years before CLL diagnosis, often in the absence of elevated lymphocyte counts,” they wrote. “Remarkably, some patients with CLL requiring treatment and clinical transformation to an aggressive B-cell lymphoma displayed considerable skewing in the IGH gene repertoire even 16 years before CLL diagnosis.”

Patients with a prediagnostic IGHV-unmutated dominant clonotype had significantly shorter overall survival after CLL diagnosis than did those with an IGHV-mutated clonotype, they noted.

“Furthermore, at early timepoints (>10 years before diagnosis), patients with a high dominant clonotype frequency were more likely to be IGHV mutated, whereas closer to diagnosis this tendency was lost, indicating that the prediagnostic phase may be even longer than 16 years for [mutated] CLL patients,” they added.

The investigators also found that:

• Twenty-five patients carried stereotyped BcR IG up to 17 years prior to CLL diagnosis, and of these, 10 clonotypes were assigned to minor subsets and 15 to major CLL subsets. Among the latter, 14 of the 15 belonged to high-risk subsets, and most of those showed a trend for faster disease evolution.
• High frequency of the dominant clonotype was evident in samples obtained less than 6 years before diagnosis, whereas high-risk stereotyped clonotypes found longer before diagnosis (as early as 16 years) tended to have a lower dominant clonotype frequency (<20% of IGH gene repertoire)
• The stereotyped BcR IG matched the clonotype at diagnosis for both patients with diagnostic material.
• No stereotyped subsets were identified among the dominant clonotypes of the healthy controls.

“To our knowledge, the dynamics of the emergence of biclonality in an MBL patient and subsequent progression to CLL have never been captured in such a convincing manner,” they noted.

The findings “extend current knowledge on the evolution of the IGH repertoire prior to CLL diagnosis, highlighting that even high-risk CLL subtypes may display a prolonged indolent preclinical stage,” they added, speculating that “somatic genetic aberrations, (auto)stimulation, epigenetic and/or microenvironmental influences are required for the transformation into overt CLL.”

The investigators also noted that since the observed skewing in the IGH gene repertoire often occurs prior to B-cell lymphocytosis, they consider the findings “a novel extension to the characterization of MBL.”

“Further studies may prove invaluable in the clinical distinction between ‘progressing’ MBL versus ‘stable’ MBL. Notwithstanding the above, we emphasize that early detection is only warranted if it provides clear benefits to patient care,” they concluded.

In a related commentary, Gerald Marti, MD, PhD, of the National Heart, Lung, and Blood Institute, emphasized that the findings “represent the earliest detection of a clonotypic precursor cell for CLL.” .

They also raise new questions and point to new directions for research, Dr. Marti noted.

“Where do we go from here? CLL has a long evolutionary history in which early branching may start as an oligoclonal process (antigen stimulation) and include driver mutations,” he wrote. “A long-term analysis of the B-cell repertoire in familial CLL might shed light on this process. Further clarification of the mechanisms of age-related immune senescence is also of interest.”

The study authors and Dr. Marti reported having no competing financial interests.