AVAHO

The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell product for the treatment of adults with certain types of relapsed or refractory large B-cell lymphoma who relapse or fail to respond to at least two systemic treatments.

The new approval comes with a risk evaluation and mitigation strategy (REMS) because of the risk for serious adverse events, including cytokine release syndrome (CRS).

The product, from Juno Therapeutics, a Bristol Myers Squibb company, is the third gene therapy to receive FDA approval for non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma in adults, accounting for about a third of the approximately 77,000 cases diagnosed each year in the United States.

The FDA previously granted Breyanzi orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. The product is the first therapy with an RMAT designation to be licensed by the agency.

The new approval is based on efficacy and safety demonstrated in a pivotal phase 1 trial of more than 250 adults with relapsed or refractory large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%. 

“Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities,” the FDA explained. “Both CRS and neurological events can be life-threatening.”

Other side effects, which typically present within 1-2 weeks after treatment, include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system, but some side effects may occur later.

The REMS requires special certification for facilities that dispense the product and “specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi,” the FDA noted.

Breyanzi is not indicated for patients with primary central nervous system lymphoma, the FDA noted.

Facility certification involves training to recognize and manage the risks of CRS and neurologic toxicities.

A postmarketing study to further evaluate the long-term safety will also be required.

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

The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell product for the treatment of adults with certain types of relapsed or refractory large B-cell lymphoma who relapse or fail to respond to at least two systemic treatments.

The new approval comes with a risk evaluation and mitigation strategy (REMS) because of the risk for serious adverse events, including cytokine release syndrome (CRS).

The product, from Juno Therapeutics, a Bristol Myers Squibb company, is the third gene therapy to receive FDA approval for non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma in adults, accounting for about a third of the approximately 77,000 cases diagnosed each year in the United States.

The FDA previously granted Breyanzi orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. The product is the first therapy with an RMAT designation to be licensed by the agency.

The new approval is based on efficacy and safety demonstrated in a pivotal phase 1 trial of more than 250 adults with relapsed or refractory large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%. 

“Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities,” the FDA explained. “Both CRS and neurological events can be life-threatening.”

Other side effects, which typically present within 1-2 weeks after treatment, include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system, but some side effects may occur later.

The REMS requires special certification for facilities that dispense the product and “specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi,” the FDA noted.

Breyanzi is not indicated for patients with primary central nervous system lymphoma, the FDA noted.

Facility certification involves training to recognize and manage the risks of CRS and neurologic toxicities.

A postmarketing study to further evaluate the long-term safety will also be required.

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

The Food and Drug Administration has approved lisocabtagene maraleucel (Breyanzi), a chimeric antigen receptor (CAR) T-cell product for the treatment of adults with certain types of relapsed or refractory large B-cell lymphoma who relapse or fail to respond to at least two systemic treatments.

The new approval comes with a risk evaluation and mitigation strategy (REMS) because of the risk for serious adverse events, including cytokine release syndrome (CRS).

The product, from Juno Therapeutics, a Bristol Myers Squibb company, is the third gene therapy to receive FDA approval for non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common type of non-Hodgkin lymphoma in adults, accounting for about a third of the approximately 77,000 cases diagnosed each year in the United States.

The FDA previously granted Breyanzi orphan drug, regenerative medicine advanced therapy (RMAT), and breakthrough therapy designations. The product is the first therapy with an RMAT designation to be licensed by the agency.

The new approval is based on efficacy and safety demonstrated in a pivotal phase 1 trial of more than 250 adults with relapsed or refractory large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%. 

“Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities,” the FDA explained. “Both CRS and neurological events can be life-threatening.”

Other side effects, which typically present within 1-2 weeks after treatment, include hypersensitivity reactions, serious infections, low blood cell counts, and a weakened immune system, but some side effects may occur later.

The REMS requires special certification for facilities that dispense the product and “specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi,” the FDA noted.

Breyanzi is not indicated for patients with primary central nervous system lymphoma, the FDA noted.

Facility certification involves training to recognize and manage the risks of CRS and neurologic toxicities.

A postmarketing study to further evaluate the long-term safety will also be required.

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

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

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

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

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

Researchers say women with type 2 diabetes treated with metformin had a reduced rate of the most common type of breast cancer, estrogen receptor (ER)–positive tumors, during a median follow-up of nearly 9 years in a prospective study of more than 44,000 individuals in the United States.

Conversely, the results also showed higher rates of ER-negative and triple-negative breast cancer among women with type 2 diabetes who received metformin, although case numbers were small.

“Our conclusion that having type 2 diabetes increases the risk of developing breast cancer but taking metformin may protect against developing ER-positive breast cancer – but not other types of breast cancer – is biologically plausible and supported by our results, even though some [endpoints] are not statistically significant,” senior author Dale P. Sandler, PhD, chief of the epidemiology branch, National Institute of Environmental Health Sciences, Research Triangle Park, N.C., said in an interview.

“Among our findings that are not statistically significant are several that helped us get a better picture of the relationships between type 2 diabetes, metformin treatment, and breast cancer risk,” Dr. Sandler added.

The results were published online Jan. 28 in Annals of Oncology by Yong-Moon Mark Park, MD, PhD, now an epidemiologist at the University of Arkansas for Medical Sciences in Little Rock, and colleagues.

Sara P. Cate, MD, a breast cancer surgeon at Mount Sinai Medical Center in New York, who was not involved with the study, said: “Certainly, metformin helps with weight loss, which is linked with estrogen-driven breast cancers, so this may explain why fewer patients on metformin got this type of breast cancer.”
 

A tangled web ... with no clear conclusions yet

But in an accompanying editorial, Ana E. Lohmann, MD, PhD, and Pamela J. Goodwin, MD, say that, while this is “a large, well-designed prospective cohort study,” it tells a complicated story.

“The report by Park adds to the growing evidence linking type 2 diabetes and its treatment to breast cancer risk, but definitive conclusions regarding these associations are not yet possible,” they observe.

The “largely negative” results of the new study perhaps in part occurred because the cohort included only 277 women with type 2 diabetes diagnosed with incident breast cancer, note Dr. Lohmann, of London Health Sciences Centre, University of Western Ontario, and Dr. Goodwin, of Mount Sinai Hospital, Toronto.

“Clearly, this is an important area, and additional research is needed to untangle the web of inter-related associations of type 2 diabetes, its treatment, and breast cancer risk,” they write.

Examination of the effects of metformin in studies such as the Canadian Cancer Trial Group MA.32, a phase 3 trial of over 3,500 women with hormone receptor–positive early-stage breast cancer who are being randomized to metformin or placebo for up to 5 years in addition to standard adjuvant therapy, will provide further insights, they observe. The trial is slated to be completed in February 2022.
 

Study followed women whose sisters had breast cancer 

The new data come from the Sister Study, which followed more than 50,000 women without a history of breast cancer who had sisters or half-sisters with a breast cancer diagnosis. The study, run by the NIEHS, enrolled women 35-74 years old from all 50 U.S. states and Puerto Rico in 2003-2009.

The current analysis excluded women with a history of any other type of cancer, missing data about diabetes, or an uncertain breast cancer diagnosis during the study, which left 44,541 available for study. At entry, 7% of the women had type 2 diabetes, and another 5% developed new-onset type 2 diabetes during follow-up.

Among those with diabetes, 61% received treatment with metformin either alone or with other antidiabetic drugs.

During a median follow-up of 8.6 years, 2,678 women received a diagnosis of primary breast cancer, either invasive or ductal carcinoma in situ.

In a series of multivariate analyses that adjusted for numerous potential confounders, the authors found that, overall, no association existed between diabetes and breast cancer incidence, with a hazard ratio of 0.99, compared with women without diabetes.

But, said Dr. Sandler, “there is a strong biological rationale to hypothesize that type 2 diabetes increases the risk for breast cancer, and results from earlier studies support this.”
 

Association of metformin and breast cancer

Women with type 2 diabetes who received metformin had a 14% lower rate of ER-positive breast cancer, compared with women with diabetes not taking metformin, a nonsignificant association.

Among women taking metformin for at least 10 years, the associated reduction in ER-positive breast cancer, compared with those who did not take it, was 38%, a difference that just missed significance, with a 95% confidence interval of 0.38-1.01.

In contrast, cases of ER-negative and triple-negative breast cancers increased in the women with diabetes taking metformin. The hazard ratio for ER-negative tumors showed a nonsignificant 25% relative increase in women taking metformin and a significant 74% increase in triple-negative cancers.

The editorialists note, however, that “the number of patients who were found to have triple-negative breast cancer was small [so] we cannot draw any practice-changing conclusions from it.”

In conclusion, Dr. Park and colleagues reiterate: “Our analysis is consistent with a potential protective effect of metformin and suggests that long-term use of metformin may reduce breast cancer risk associated with type 2 diabetes.”

The study received no commercial funding. Dr. Sandler, Dr. Park, Dr. Lohmann, Dr. Goodwin, and Dr. Cate have reported no relevant financial relationships.

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

The Food and Drug Administration has alerted the public to an increased risk of serious heart-related problems and cancer risk associated with the Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR), based on early results from a safety clinical trial comparing tofacitinib and tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).

The FDA is awaiting further results from the trial, but in a safety communication issued on Feb. 4, the agency advised patients not to discontinue tofacitinib without consulting their health care providers and advised health care professionals to weigh the risks and benefits when prescribing the drug and continue to follow the current prescribing information.

Tofacitinib was approved for treatment of RA in 2012 at a 5-mg dose. After this approval, the FDA required drug manufacturer Pfizer to conduct a safety clinical trial that included the 5-mg twice-daily dose and a 10-mg twice-daily dose that is currently approved only for ulcerative colitis. In addition to RA and ulcerative colitis, tofacitinib is approved for adults with active psoriatic arthritis and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis.

Pfizer announced partial results of the study, known as the ORAL Surveillance trial, in a press release on Jan. 27. The randomized trial included 4,362 RA patients aged 50 years and older who received either 5-mg or 10-mg doses of tofacitinib or a TNF inhibitor (adalimumab or etanercept).

The full results have yet to be released, but based on data from approximately 10,000 person-years for the combined tofacitinib groups and approximately 5,000 person-years for the TNF inhibitor group, the rate of major cardiovascular adverse events was significantly higher in the combined tofacitinib group, compared with the TNF inhibitor group (0.98 vs. 0.73 per 100 person-years; hazard ratio, 1.33). In addition, the rate of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNF inhibitor group (1.13 vs. 0.77 per 100 person-years; HR, 1.48).

In February 2019, the FDA issued a warning stating an increased risk of pulmonary embolism and death associated with the 10-mg twice-daily dose of tofacitinib, following interims results from the safety study.

In July 2019, the FDA added a boxed warning to tofacitinib advising of the increased risk for pulmonary embolism and death associated with the 10-mg twice-daily dose.

The FDA encouraged health care professionals and patients to report any side effects from tofacitinib or other medications through the FDA MedWatch program online or by phone at 1-800-332-1088.

Until nuances revealed, no change in practice

The preliminary study findings contain some nuances that are a bit complicated from a statistical standpoint, according to Daniel Furst, MD, professor emeritus of medicine at the University of California, Los Angeles; adjunct professor at the University of Washington, Seattle; and research professor at the University of Florence (Italy).

Updated on 2/8/2021.

The Food and Drug Administration has alerted the public to an increased risk of serious heart-related problems and cancer risk associated with the Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR), based on early results from a safety clinical trial comparing tofacitinib and tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).

The FDA is awaiting further results from the trial, but in a safety communication issued on Feb. 4, the agency advised patients not to discontinue tofacitinib without consulting their health care providers and advised health care professionals to weigh the risks and benefits when prescribing the drug and continue to follow the current prescribing information.

Tofacitinib was approved for treatment of RA in 2012 at a 5-mg dose. After this approval, the FDA required drug manufacturer Pfizer to conduct a safety clinical trial that included the 5-mg twice-daily dose and a 10-mg twice-daily dose that is currently approved only for ulcerative colitis. In addition to RA and ulcerative colitis, tofacitinib is approved for adults with active psoriatic arthritis and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis.

Pfizer announced partial results of the study, known as the ORAL Surveillance trial, in a press release on Jan. 27. The randomized trial included 4,362 RA patients aged 50 years and older who received either 5-mg or 10-mg doses of tofacitinib or a TNF inhibitor (adalimumab or etanercept).

The full results have yet to be released, but based on data from approximately 10,000 person-years for the combined tofacitinib groups and approximately 5,000 person-years for the TNF inhibitor group, the rate of major cardiovascular adverse events was significantly higher in the combined tofacitinib group, compared with the TNF inhibitor group (0.98 vs. 0.73 per 100 person-years; hazard ratio, 1.33). In addition, the rate of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNF inhibitor group (1.13 vs. 0.77 per 100 person-years; HR, 1.48).

In February 2019, the FDA issued a warning stating an increased risk of pulmonary embolism and death associated with the 10-mg twice-daily dose of tofacitinib, following interims results from the safety study.

In July 2019, the FDA added a boxed warning to tofacitinib advising of the increased risk for pulmonary embolism and death associated with the 10-mg twice-daily dose.

The FDA encouraged health care professionals and patients to report any side effects from tofacitinib or other medications through the FDA MedWatch program online or by phone at 1-800-332-1088.

Until nuances revealed, no change in practice

The preliminary study findings contain some nuances that are a bit complicated from a statistical standpoint, according to Daniel Furst, MD, professor emeritus of medicine at the University of California, Los Angeles; adjunct professor at the University of Washington, Seattle; and research professor at the University of Florence (Italy).

Updated on 2/8/2021.

The Food and Drug Administration has alerted the public to an increased risk of serious heart-related problems and cancer risk associated with the Janus kinase inhibitor tofacitinib (Xeljanz, Xeljanz XR), based on early results from a safety clinical trial comparing tofacitinib and tumor necrosis factor inhibitors in patients with rheumatoid arthritis (RA).

The FDA is awaiting further results from the trial, but in a safety communication issued on Feb. 4, the agency advised patients not to discontinue tofacitinib without consulting their health care providers and advised health care professionals to weigh the risks and benefits when prescribing the drug and continue to follow the current prescribing information.

Tofacitinib was approved for treatment of RA in 2012 at a 5-mg dose. After this approval, the FDA required drug manufacturer Pfizer to conduct a safety clinical trial that included the 5-mg twice-daily dose and a 10-mg twice-daily dose that is currently approved only for ulcerative colitis. In addition to RA and ulcerative colitis, tofacitinib is approved for adults with active psoriatic arthritis and patients aged 2 years or older with active polyarticular course juvenile idiopathic arthritis.

Pfizer announced partial results of the study, known as the ORAL Surveillance trial, in a press release on Jan. 27. The randomized trial included 4,362 RA patients aged 50 years and older who received either 5-mg or 10-mg doses of tofacitinib or a TNF inhibitor (adalimumab or etanercept).

The full results have yet to be released, but based on data from approximately 10,000 person-years for the combined tofacitinib groups and approximately 5,000 person-years for the TNF inhibitor group, the rate of major cardiovascular adverse events was significantly higher in the combined tofacitinib group, compared with the TNF inhibitor group (0.98 vs. 0.73 per 100 person-years; hazard ratio, 1.33). In addition, the rate of adjudicated malignancies was significantly higher in the tofacitinib group, compared with the TNF inhibitor group (1.13 vs. 0.77 per 100 person-years; HR, 1.48).

In February 2019, the FDA issued a warning stating an increased risk of pulmonary embolism and death associated with the 10-mg twice-daily dose of tofacitinib, following interims results from the safety study.

In July 2019, the FDA added a boxed warning to tofacitinib advising of the increased risk for pulmonary embolism and death associated with the 10-mg twice-daily dose.

The FDA encouraged health care professionals and patients to report any side effects from tofacitinib or other medications through the FDA MedWatch program online or by phone at 1-800-332-1088.

Until nuances revealed, no change in practice

The preliminary study findings contain some nuances that are a bit complicated from a statistical standpoint, according to Daniel Furst, MD, professor emeritus of medicine at the University of California, Los Angeles; adjunct professor at the University of Washington, Seattle; and research professor at the University of Florence (Italy).

Updated on 2/8/2021.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

Machine learning models that use routine data present in the electronic health record have identified new risk factors for early-onset colorectal cancer (CRC), according to a new study.

Copyright University of Florida

The models found that hypertension, cough, and asthma, among other factors, were important in explaining the risk of early-onset CRC. For some factors, associations emerged up to 5 years before diagnosis.

These findings were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract PR-10).

“The incidence of early-onset CRC has been rising 2% annually since 1994,” noted Michael B. Quillen, one of the study authors and a medical student at the University of Florida, Gainesville.

Inherited genetic syndromes and predisposing conditions such as inflammatory bowel disease account for about half of cases in this age group, but factors explaining the other half remain a mystery.

To shed light in this area, the investigators undertook a study of patients aged 50 years or younger from the OneFlorida Clinical Research Consortium who had at least 2 years of EHR data. This included 783 cases with CRC and 8,981 incidence density-matched controls, with both groups having a mean age of 36 years.

The patients were split into colon cancer and rectal cancer cohorts, and then further divided into four prediction windows, Mr. Quillen explained. Each prediction window started with the patient’s first recorded encounter date in the EHR and ended at 0, 1, 3, or 5 years before the date of diagnosis.

The investigators used machine-learning models to determine what features (e.g., diagnoses, procedures, demographics) were important in determining risk.

Results were expressed in charts that ranked the features by their SHAP (Shapley Additive Explanations) values, which reflect the average impact of a feature on the magnitude of model output.
 

Results: Top models and features

The top-performing models had areas under the curve of 0.61-0.75 for colon cancer risk, and 0.62-0.73 for rectal cancer risk, reported T. Maxwell Parker, another study author and medical student at the University of Florida, Gainesville.

Copyright University of Florida

For colon cancer, the top features for the 0-year cohort included some highly specific symptoms that would be expected in patients close to the diagnostic date: abdominal pain, anemia, blood in the stool, and various procedures such as CT scans. “These do not need a machine learning algorithm to identify,” Mr. Parker acknowledged.

However, there were also two noteworthy features present – cough and primary hypertension – that became the top features in the 1-year and 3-year cohorts, then dropped out in the 5-year cohort.

Other features that became important moving farther out from the diagnostic date of colon cancer, across the windows studied, were chronic sinusitis, atopic dermatitis, asthma, and upper-respiratory infection.

For rectal cancer, some previously identified factors – immune conditions related to infectious disease (HIV and anogenital warts associated with human papillomavirus) as well as amoxicillin therapy – were prominent in the 0-year cohort and became increasingly important going farther out from the diagnostic date.

Obesity was the top feature in the 3-year cohort, and asthma became important in that cohort as well.

None of the rectal cancer models tested performed well at identifying important features in the 5-year cohort.

The investigators are exploring hypotheses to explain how the identified features, especially the new ones such as hypertension and cough, might contribute to CRC carcinogenesis in young adults, according to Mr. Parker. As inclusion of older patients could confound associations, research restricted to those aged 50 years and younger may be necessary.

“We would like to validate these model findings in a second independent data set, and if they are validated, we would consider a prospective cohort study with those features,” Mr. Parker said. The team also plans to refine the models with the aim of improving their areas under the curve.

Thereafter, the team hopes to explore ways for implementing the findings clinically to support screening, which will require consideration of the context, Mr. Parker concluded. “Should we use high-sensitivity or low-specificity models for screening, or do we use the balance of both? Also, different models may be suitable for different situations,” he said.

Mr. Parker and Mr. Quillen disclosed no conflicts of interest. The study did not receive specific funding.

Machine learning models that use routine data present in the electronic health record have identified new risk factors for early-onset colorectal cancer (CRC), according to a new study.

Copyright University of Florida

The models found that hypertension, cough, and asthma, among other factors, were important in explaining the risk of early-onset CRC. For some factors, associations emerged up to 5 years before diagnosis.

These findings were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract PR-10).

“The incidence of early-onset CRC has been rising 2% annually since 1994,” noted Michael B. Quillen, one of the study authors and a medical student at the University of Florida, Gainesville.

Inherited genetic syndromes and predisposing conditions such as inflammatory bowel disease account for about half of cases in this age group, but factors explaining the other half remain a mystery.

To shed light in this area, the investigators undertook a study of patients aged 50 years or younger from the OneFlorida Clinical Research Consortium who had at least 2 years of EHR data. This included 783 cases with CRC and 8,981 incidence density-matched controls, with both groups having a mean age of 36 years.

The patients were split into colon cancer and rectal cancer cohorts, and then further divided into four prediction windows, Mr. Quillen explained. Each prediction window started with the patient’s first recorded encounter date in the EHR and ended at 0, 1, 3, or 5 years before the date of diagnosis.

The investigators used machine-learning models to determine what features (e.g., diagnoses, procedures, demographics) were important in determining risk.

Results were expressed in charts that ranked the features by their SHAP (Shapley Additive Explanations) values, which reflect the average impact of a feature on the magnitude of model output.
 

Results: Top models and features

The top-performing models had areas under the curve of 0.61-0.75 for colon cancer risk, and 0.62-0.73 for rectal cancer risk, reported T. Maxwell Parker, another study author and medical student at the University of Florida, Gainesville.

Copyright University of Florida

For colon cancer, the top features for the 0-year cohort included some highly specific symptoms that would be expected in patients close to the diagnostic date: abdominal pain, anemia, blood in the stool, and various procedures such as CT scans. “These do not need a machine learning algorithm to identify,” Mr. Parker acknowledged.

However, there were also two noteworthy features present – cough and primary hypertension – that became the top features in the 1-year and 3-year cohorts, then dropped out in the 5-year cohort.

Other features that became important moving farther out from the diagnostic date of colon cancer, across the windows studied, were chronic sinusitis, atopic dermatitis, asthma, and upper-respiratory infection.

For rectal cancer, some previously identified factors – immune conditions related to infectious disease (HIV and anogenital warts associated with human papillomavirus) as well as amoxicillin therapy – were prominent in the 0-year cohort and became increasingly important going farther out from the diagnostic date.

Obesity was the top feature in the 3-year cohort, and asthma became important in that cohort as well.

None of the rectal cancer models tested performed well at identifying important features in the 5-year cohort.

The investigators are exploring hypotheses to explain how the identified features, especially the new ones such as hypertension and cough, might contribute to CRC carcinogenesis in young adults, according to Mr. Parker. As inclusion of older patients could confound associations, research restricted to those aged 50 years and younger may be necessary.

“We would like to validate these model findings in a second independent data set, and if they are validated, we would consider a prospective cohort study with those features,” Mr. Parker said. The team also plans to refine the models with the aim of improving their areas under the curve.

Thereafter, the team hopes to explore ways for implementing the findings clinically to support screening, which will require consideration of the context, Mr. Parker concluded. “Should we use high-sensitivity or low-specificity models for screening, or do we use the balance of both? Also, different models may be suitable for different situations,” he said.

Mr. Parker and Mr. Quillen disclosed no conflicts of interest. The study did not receive specific funding.

Machine learning models that use routine data present in the electronic health record have identified new risk factors for early-onset colorectal cancer (CRC), according to a new study.

Copyright University of Florida

The models found that hypertension, cough, and asthma, among other factors, were important in explaining the risk of early-onset CRC. For some factors, associations emerged up to 5 years before diagnosis.

These findings were reported at the AACR Virtual Special Conference: Artificial Intelligence, Diagnosis, and Imaging (Abstract PR-10).

“The incidence of early-onset CRC has been rising 2% annually since 1994,” noted Michael B. Quillen, one of the study authors and a medical student at the University of Florida, Gainesville.

Inherited genetic syndromes and predisposing conditions such as inflammatory bowel disease account for about half of cases in this age group, but factors explaining the other half remain a mystery.

To shed light in this area, the investigators undertook a study of patients aged 50 years or younger from the OneFlorida Clinical Research Consortium who had at least 2 years of EHR data. This included 783 cases with CRC and 8,981 incidence density-matched controls, with both groups having a mean age of 36 years.

The patients were split into colon cancer and rectal cancer cohorts, and then further divided into four prediction windows, Mr. Quillen explained. Each prediction window started with the patient’s first recorded encounter date in the EHR and ended at 0, 1, 3, or 5 years before the date of diagnosis.

The investigators used machine-learning models to determine what features (e.g., diagnoses, procedures, demographics) were important in determining risk.

Results were expressed in charts that ranked the features by their SHAP (Shapley Additive Explanations) values, which reflect the average impact of a feature on the magnitude of model output.
 

Results: Top models and features

The top-performing models had areas under the curve of 0.61-0.75 for colon cancer risk, and 0.62-0.73 for rectal cancer risk, reported T. Maxwell Parker, another study author and medical student at the University of Florida, Gainesville.

Copyright University of Florida

For colon cancer, the top features for the 0-year cohort included some highly specific symptoms that would be expected in patients close to the diagnostic date: abdominal pain, anemia, blood in the stool, and various procedures such as CT scans. “These do not need a machine learning algorithm to identify,” Mr. Parker acknowledged.

However, there were also two noteworthy features present – cough and primary hypertension – that became the top features in the 1-year and 3-year cohorts, then dropped out in the 5-year cohort.

Other features that became important moving farther out from the diagnostic date of colon cancer, across the windows studied, were chronic sinusitis, atopic dermatitis, asthma, and upper-respiratory infection.

For rectal cancer, some previously identified factors – immune conditions related to infectious disease (HIV and anogenital warts associated with human papillomavirus) as well as amoxicillin therapy – were prominent in the 0-year cohort and became increasingly important going farther out from the diagnostic date.

Obesity was the top feature in the 3-year cohort, and asthma became important in that cohort as well.

None of the rectal cancer models tested performed well at identifying important features in the 5-year cohort.

The investigators are exploring hypotheses to explain how the identified features, especially the new ones such as hypertension and cough, might contribute to CRC carcinogenesis in young adults, according to Mr. Parker. As inclusion of older patients could confound associations, research restricted to those aged 50 years and younger may be necessary.

“We would like to validate these model findings in a second independent data set, and if they are validated, we would consider a prospective cohort study with those features,” Mr. Parker said. The team also plans to refine the models with the aim of improving their areas under the curve.

Thereafter, the team hopes to explore ways for implementing the findings clinically to support screening, which will require consideration of the context, Mr. Parker concluded. “Should we use high-sensitivity or low-specificity models for screening, or do we use the balance of both? Also, different models may be suitable for different situations,” he said.

Mr. Parker and Mr. Quillen disclosed no conflicts of interest. The study did not receive specific funding.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

A third of patients with COVID-19 and thoracic malignancies die, according to updated results from the TERAVOLT registry.

The risk of death was similar across racial and ethnic groups. Factors associated with an increased risk of death were male sex, older age, worse performance scores, and four or more metastatic sites.

“Death rates remain high at 33%, underscoring the importance of COVID-19 vaccination in patients with thoracic cancers, when available,” said Umit Tapan, MD, of Boston University.

Dr. Tapan presented the TERAVOLT update at the 2020 World Congress on Lung Cancer (Abstract P09.18), which was rescheduled for January 2021.

The TERAVOLT registry is a multicenter, observational study with a cross-sectional component and a longitudinal cohort component.

The registry includes patients who have thoracic cancers – non–small cell lung cancer (NSCLC), small cell lung cancer, mesothelioma, thymic epithelial tumors, and other pulmonary neuroendocrine neoplasms – and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms.

Clinical data were extracted from medical records of consecutive patients from Jan. 1, 2020, and will be collected until the end of pandemic, as declared by the World Health Organization. Data collected include demographics, oncologic history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes.

“The overarching goals of this consortium are to provide data for guidance to oncology professionals on managing patients with thoracic malignancies while understanding the risk factors for morbidity and mortality from this novel virus,” Dr. Tapan said.

Data from TERAVOLT were previously presented at AACR, ASCO, and ESMO last year, as well as published in The Lancet Oncology.

Updated results

Dr. Tapan presented data on 1,011 patients from 120 centers in 19 countries. The patients’ median age was 68 years (range, 28-95 years), and more than half were male (58%). Most patients (72%) were White, 20% were Hispanic/Latino, and 8% were Black/African American.

Most patients had NSCLC (82%), and most had stage IV disease (68%). Patients had received a median of one prior line of therapy.

As in earlier reports of TERAVOLT data, the mortality rate was 33%.

In a multivariate analysis, the following characteristics were associated with an increased risk of death:

• Male sex (odds ratio, 1.4).
• Older age (per 10 years; OR, 1.21).
• Performance score of 1 (OR, 1.73), 2 (OR, 4.74), and 3/4 (OR, 10.7).
• Four or more metastatic sites (OR, 3.05).

The following characteristics were associated with an increased risk of hospitalization in a multivariate analysis:

• Male sex (OR, 1.67).
• Older age (per 10 years; OR, 1.24).
• Performance score of 2 (OR, 4.47) and 3/4 (OR, 9.63).
• Four or more metastatic sites (OR, 4.0).
• Thymic carcinoma (OR, 3.58).
• Receiving radiation (OR, 2.1).

Race and ethnicity did not seem to affect the risk of death or hospitalization, “but we plan to conduct further analysis,” Dr. Tapan said.

Roxana Reyes, MD, of Hospital Clínic de Barcelona, said her hospital sees patients with lung cancer at high risk for COVID-19, but there is no screening program in place.

“We use medical consultations to focus on early diagnosis. We treat COVID-19 complications but lose a lot of patients. There is an opportunity to be found to find these patients sooner,” Dr. Reyes said.

She noted that COVID-19 will likely last a long time, and therefore “we have to protect against it and continue to diagnose lung cancer at earlier stages.”

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. Dr. Tapan has no relevant disclosures. The TERAVOLT registry is funded, in part, by the International Association for the Study of Lung Cancer.

In the first ever placebo-controlled phase 3 trial in patients with relapsed mesothelioma, immunotherapy with nivolumab significantly improved both overall survival (OS) and progression-free survival (PFS).

The CONFIRM trial involved 330 previously treated patients with mesothelioma who were randomly assigned to nivolumab or placebo for 1 year or until progression or unacceptable toxicity.

Although recruitment to the study was stopped early because of the COVID-19 pandemic, enough data accrued to show that nivolumab improved overall survival by 28% over placebo, and increased PFS by 39%.

“Nivolumab was deemed a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” said principal investigator Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester (England).

He presented the results at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Rina Hui, MD, PhD, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, who was not involved in the study, said that these results had been a “long time coming.”

CONFIRM has added “important, encouraging data on immunotherapy in the salvage setting,” Dr. Hui said, noting that two-thirds of patients had received two or more prior lines of therapy.

Dr. Fennel noted that “a significant clinical benefit was observed in the epithelioid subtype” of the disease but not in patients with nonepithelioid disease.

However, there was “no evidence” to support programmed death–ligand 1 (PD-L1) expression as predictive of outcomes, he added, which does appear to be the case in some trials on lung cancer and other tumors.

Commenting on these observations, Dr. Hui said that PD-L1 as a predictive biomarker in mesothelioma has been “controversial,” and she emphasized that the results from CONFIRM indicate “no evidence of PD-L1 being predictive.”

However, Dr. Hui questioned the other observation that clinical benefit appeared to be seen only in the epithelioid subtype.

She emphasized that nonepithelioid disease is known to be a “more aggressive, chemoresistant subtype ... with a steep decline in the survival curves.

“Therefore, a lot of patients would not have made it to a subsequent-line clinical trial, explaining why there were only 12% in the CONFIRM study,” and so the sample size may be “too small to detect a difference in outcome,” Dr. Hui said.

Consequently, Dr. Hui said she “would not deny patients with nonepithelioid histology from considering nivolumab in the salvage setting.”

She argued that there was “no clear predictive biomarker for patient selection” emerging from the CONFIRM data.

She agreed that, in patients with mesothelioma who have progressed following platinum/pemetrexed-based chemotherapy as in the first line, “monotherapy nivolumab now can be considered as a treatment option in the second- ... or third-line setting, after second-line chemotherapy”.

However, outstanding questions remain, including whether nivolumab “provides better outcomes than second-line single agent chemotherapy or second-line gemcitabine with the [vascular endothelial growth factor receptor] inhibitor ramucirumab.”

It may also be that nivolumab plus ipilimumab might be superior to nivolumab alone in the salvage setting.

But a more fundamental question is what should be considered for salvage therapy if nivolumab and ipilimumab have already been used in the first-line setting, Dr. Hui said.

Results of first-line immunotherapy combination trials are “eagerly awaited ... to determine and develop other salvage treatments,” she commented.

Responding on Twitter, Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust in Royal Tunbridge Wells, England, echoed these comments, saying that the results were “very exciting,” but he also “can’t wait to see the first-line chemo–immunotherapy data.”

Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, commented on Twitter that there was “not a lot of safety data” in the presentation and awaits their eventual publication.

He added that it is “good to have a positive trial” in relapsed mesothelioma, “though the first-line studies will decrease the eventual impact as immunotherapy becomes involved earlier in treatment.”

 

Details of the CONFIRM results 

Relapsed mesothelioma is an “unmet need,” and, until now, “there have been no phase 3 trials which have demonstrated improved overall survival,” Dr. Fennell said in his presentation.

However, three phase 2 trials have shown that immune checkpoint targeting via PD-1 has shown useful clinical activity as a monotherapy in the relapsed setting, and one of these trials has led to approval of nivolumab in Japan for this indication.

CONFIRM was an investigator-initiated phase 3 trial in patients with relapsed mesothelioma who had received more than one prior line of therapy and had a good performance status.

Recruitment began in April 2017, and the “target sample size was 336 patients,” Dr. Fennell said, but the trial was “halted at 332 patients (in March 2020) due to the peaking of the COVID-19 pandemic in the U.K.”

“However, at the time, it was felt there were sufficient events” to justify the current analysis of the coprimary endpoints of PFS and OS, despite the latter being 59 events short of the target of 291.

Dr. Fennell said that baseline characteristics were “generally well balanced” between the nivolumab (n = 221) and placebo (n = 111) arms.

However, there were more patients with a PD-L1 tumor proportion score (TPS) of at least 1% among the patients given nivolumab, at 37% versus 29% in the placebo arm.

After a median follow-up of 17.1 months in the nivolumab arm and 14.2 months in the placebo group, overall survival was significantly longer with the active treatment, at 9.2 months versus 6.6 months with placebo (hazard ratio, 0.72; P = .018).

The proportion of patients alive at 12 months was 39.5% in the nivolumab group and 26.9% in patients given placebo. Investigator-assessed PFS was also significantly longer with nivolumab, at 3.0 months versus 1.8 months with placebo (HR, 0.61; P < .001).

The proportion of patients disease free at 12 months was 14.5% with active treatment versus 4.9% months with the placebo.

“The role for PD-L1 as a potential biomarker was assessed,” Dr. Fennell said, using the Dako 22C3 antibody, with 150 nivolumab and 84 placebo patients divided into those with a TPS <1% or ≥1%.

He noted that PD-L1 expression in the tumor “did not predict survival for patients in the CONFIRM trial,” with neither PD-L1 positive nor PD-L1 negative patients demonstrating a significant improvement in overall survival with nivolumab vs placebo.

“For histology, epithelioid mesothelioma patients benefited from nivolumab,” Dr. Fennell continued, with a hazard ratio for death of 0.71 versus placebo (P = .021). “However, for the nonepithelioid subgroup, in this immature survival analysis ... the P value was not significant,” but this was a small subgroup of patients (12% in both nivolumab and placebo groups).

The safety analysis revealed that the proportion of patients with any serious adverse events, of any grade or grade 3 or higher, was almost identical between the active and placebo arms, Dr. Fennel reported. There were five deaths (3.6%) related to a serious adverse event in the nivolumab arm and four (5.3%) in the placebo group.

This research was funded by the Stand Up to Cancer campaign for Cancer Research UK, supported by Cancer Research UK core funding at the Southampton Clinical Trials Unit, and investigator-initiated support from Bristol-Myers Squibb for free drug labeling and distribution and funding for RECIST reporting. Dr. Fennell reported relationships with Astex Therapeutics, AstraZeneca, Atara Biotherapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Inventiva, Lab 21, Merck, and Roche. Dr. Hui reported relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Seagen.

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

In the first ever placebo-controlled phase 3 trial in patients with relapsed mesothelioma, immunotherapy with nivolumab significantly improved both overall survival (OS) and progression-free survival (PFS).

The CONFIRM trial involved 330 previously treated patients with mesothelioma who were randomly assigned to nivolumab or placebo for 1 year or until progression or unacceptable toxicity.

Although recruitment to the study was stopped early because of the COVID-19 pandemic, enough data accrued to show that nivolumab improved overall survival by 28% over placebo, and increased PFS by 39%.

“Nivolumab was deemed a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” said principal investigator Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester (England).

He presented the results at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Rina Hui, MD, PhD, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, who was not involved in the study, said that these results had been a “long time coming.”

CONFIRM has added “important, encouraging data on immunotherapy in the salvage setting,” Dr. Hui said, noting that two-thirds of patients had received two or more prior lines of therapy.

Dr. Fennel noted that “a significant clinical benefit was observed in the epithelioid subtype” of the disease but not in patients with nonepithelioid disease.

However, there was “no evidence” to support programmed death–ligand 1 (PD-L1) expression as predictive of outcomes, he added, which does appear to be the case in some trials on lung cancer and other tumors.

Commenting on these observations, Dr. Hui said that PD-L1 as a predictive biomarker in mesothelioma has been “controversial,” and she emphasized that the results from CONFIRM indicate “no evidence of PD-L1 being predictive.”

However, Dr. Hui questioned the other observation that clinical benefit appeared to be seen only in the epithelioid subtype.

She emphasized that nonepithelioid disease is known to be a “more aggressive, chemoresistant subtype ... with a steep decline in the survival curves.

“Therefore, a lot of patients would not have made it to a subsequent-line clinical trial, explaining why there were only 12% in the CONFIRM study,” and so the sample size may be “too small to detect a difference in outcome,” Dr. Hui said.

Consequently, Dr. Hui said she “would not deny patients with nonepithelioid histology from considering nivolumab in the salvage setting.”

She argued that there was “no clear predictive biomarker for patient selection” emerging from the CONFIRM data.

She agreed that, in patients with mesothelioma who have progressed following platinum/pemetrexed-based chemotherapy as in the first line, “monotherapy nivolumab now can be considered as a treatment option in the second- ... or third-line setting, after second-line chemotherapy”.

However, outstanding questions remain, including whether nivolumab “provides better outcomes than second-line single agent chemotherapy or second-line gemcitabine with the [vascular endothelial growth factor receptor] inhibitor ramucirumab.”

It may also be that nivolumab plus ipilimumab might be superior to nivolumab alone in the salvage setting.

But a more fundamental question is what should be considered for salvage therapy if nivolumab and ipilimumab have already been used in the first-line setting, Dr. Hui said.

Results of first-line immunotherapy combination trials are “eagerly awaited ... to determine and develop other salvage treatments,” she commented.

Responding on Twitter, Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust in Royal Tunbridge Wells, England, echoed these comments, saying that the results were “very exciting,” but he also “can’t wait to see the first-line chemo–immunotherapy data.”

Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, commented on Twitter that there was “not a lot of safety data” in the presentation and awaits their eventual publication.

He added that it is “good to have a positive trial” in relapsed mesothelioma, “though the first-line studies will decrease the eventual impact as immunotherapy becomes involved earlier in treatment.”

 

Details of the CONFIRM results 

Relapsed mesothelioma is an “unmet need,” and, until now, “there have been no phase 3 trials which have demonstrated improved overall survival,” Dr. Fennell said in his presentation.

However, three phase 2 trials have shown that immune checkpoint targeting via PD-1 has shown useful clinical activity as a monotherapy in the relapsed setting, and one of these trials has led to approval of nivolumab in Japan for this indication.

CONFIRM was an investigator-initiated phase 3 trial in patients with relapsed mesothelioma who had received more than one prior line of therapy and had a good performance status.

Recruitment began in April 2017, and the “target sample size was 336 patients,” Dr. Fennell said, but the trial was “halted at 332 patients (in March 2020) due to the peaking of the COVID-19 pandemic in the U.K.”

“However, at the time, it was felt there were sufficient events” to justify the current analysis of the coprimary endpoints of PFS and OS, despite the latter being 59 events short of the target of 291.

Dr. Fennell said that baseline characteristics were “generally well balanced” between the nivolumab (n = 221) and placebo (n = 111) arms.

However, there were more patients with a PD-L1 tumor proportion score (TPS) of at least 1% among the patients given nivolumab, at 37% versus 29% in the placebo arm.

After a median follow-up of 17.1 months in the nivolumab arm and 14.2 months in the placebo group, overall survival was significantly longer with the active treatment, at 9.2 months versus 6.6 months with placebo (hazard ratio, 0.72; P = .018).

The proportion of patients alive at 12 months was 39.5% in the nivolumab group and 26.9% in patients given placebo. Investigator-assessed PFS was also significantly longer with nivolumab, at 3.0 months versus 1.8 months with placebo (HR, 0.61; P < .001).

The proportion of patients disease free at 12 months was 14.5% with active treatment versus 4.9% months with the placebo.

“The role for PD-L1 as a potential biomarker was assessed,” Dr. Fennell said, using the Dako 22C3 antibody, with 150 nivolumab and 84 placebo patients divided into those with a TPS <1% or ≥1%.

He noted that PD-L1 expression in the tumor “did not predict survival for patients in the CONFIRM trial,” with neither PD-L1 positive nor PD-L1 negative patients demonstrating a significant improvement in overall survival with nivolumab vs placebo.

“For histology, epithelioid mesothelioma patients benefited from nivolumab,” Dr. Fennell continued, with a hazard ratio for death of 0.71 versus placebo (P = .021). “However, for the nonepithelioid subgroup, in this immature survival analysis ... the P value was not significant,” but this was a small subgroup of patients (12% in both nivolumab and placebo groups).

The safety analysis revealed that the proportion of patients with any serious adverse events, of any grade or grade 3 or higher, was almost identical between the active and placebo arms, Dr. Fennel reported. There were five deaths (3.6%) related to a serious adverse event in the nivolumab arm and four (5.3%) in the placebo group.

This research was funded by the Stand Up to Cancer campaign for Cancer Research UK, supported by Cancer Research UK core funding at the Southampton Clinical Trials Unit, and investigator-initiated support from Bristol-Myers Squibb for free drug labeling and distribution and funding for RECIST reporting. Dr. Fennell reported relationships with Astex Therapeutics, AstraZeneca, Atara Biotherapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Inventiva, Lab 21, Merck, and Roche. Dr. Hui reported relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Seagen.

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

In the first ever placebo-controlled phase 3 trial in patients with relapsed mesothelioma, immunotherapy with nivolumab significantly improved both overall survival (OS) and progression-free survival (PFS).

The CONFIRM trial involved 330 previously treated patients with mesothelioma who were randomly assigned to nivolumab or placebo for 1 year or until progression or unacceptable toxicity.

Although recruitment to the study was stopped early because of the COVID-19 pandemic, enough data accrued to show that nivolumab improved overall survival by 28% over placebo, and increased PFS by 39%.

“Nivolumab was deemed a safe and effective treatment and should be considered a new treatment option for patients with relapsed mesothelioma,” said principal investigator Dean A. Fennell, MD, PhD, professor and consultant in thoracic medical oncology, University of Leicester (England).

He presented the results at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Rina Hui, MD, PhD, Crown Princess Mary Cancer Centre, Westmead Hospital, Sydney, who was not involved in the study, said that these results had been a “long time coming.”

CONFIRM has added “important, encouraging data on immunotherapy in the salvage setting,” Dr. Hui said, noting that two-thirds of patients had received two or more prior lines of therapy.

Dr. Fennel noted that “a significant clinical benefit was observed in the epithelioid subtype” of the disease but not in patients with nonepithelioid disease.

However, there was “no evidence” to support programmed death–ligand 1 (PD-L1) expression as predictive of outcomes, he added, which does appear to be the case in some trials on lung cancer and other tumors.

Commenting on these observations, Dr. Hui said that PD-L1 as a predictive biomarker in mesothelioma has been “controversial,” and she emphasized that the results from CONFIRM indicate “no evidence of PD-L1 being predictive.”

However, Dr. Hui questioned the other observation that clinical benefit appeared to be seen only in the epithelioid subtype.

She emphasized that nonepithelioid disease is known to be a “more aggressive, chemoresistant subtype ... with a steep decline in the survival curves.

“Therefore, a lot of patients would not have made it to a subsequent-line clinical trial, explaining why there were only 12% in the CONFIRM study,” and so the sample size may be “too small to detect a difference in outcome,” Dr. Hui said.

Consequently, Dr. Hui said she “would not deny patients with nonepithelioid histology from considering nivolumab in the salvage setting.”

She argued that there was “no clear predictive biomarker for patient selection” emerging from the CONFIRM data.

She agreed that, in patients with mesothelioma who have progressed following platinum/pemetrexed-based chemotherapy as in the first line, “monotherapy nivolumab now can be considered as a treatment option in the second- ... or third-line setting, after second-line chemotherapy”.

However, outstanding questions remain, including whether nivolumab “provides better outcomes than second-line single agent chemotherapy or second-line gemcitabine with the [vascular endothelial growth factor receptor] inhibitor ramucirumab.”

It may also be that nivolumab plus ipilimumab might be superior to nivolumab alone in the salvage setting.

But a more fundamental question is what should be considered for salvage therapy if nivolumab and ipilimumab have already been used in the first-line setting, Dr. Hui said.

Results of first-line immunotherapy combination trials are “eagerly awaited ... to determine and develop other salvage treatments,” she commented.

Responding on Twitter, Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust in Royal Tunbridge Wells, England, echoed these comments, saying that the results were “very exciting,” but he also “can’t wait to see the first-line chemo–immunotherapy data.”

Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, commented on Twitter that there was “not a lot of safety data” in the presentation and awaits their eventual publication.

He added that it is “good to have a positive trial” in relapsed mesothelioma, “though the first-line studies will decrease the eventual impact as immunotherapy becomes involved earlier in treatment.”

 

Details of the CONFIRM results 

Relapsed mesothelioma is an “unmet need,” and, until now, “there have been no phase 3 trials which have demonstrated improved overall survival,” Dr. Fennell said in his presentation.

However, three phase 2 trials have shown that immune checkpoint targeting via PD-1 has shown useful clinical activity as a monotherapy in the relapsed setting, and one of these trials has led to approval of nivolumab in Japan for this indication.

CONFIRM was an investigator-initiated phase 3 trial in patients with relapsed mesothelioma who had received more than one prior line of therapy and had a good performance status.

Recruitment began in April 2017, and the “target sample size was 336 patients,” Dr. Fennell said, but the trial was “halted at 332 patients (in March 2020) due to the peaking of the COVID-19 pandemic in the U.K.”

“However, at the time, it was felt there were sufficient events” to justify the current analysis of the coprimary endpoints of PFS and OS, despite the latter being 59 events short of the target of 291.

Dr. Fennell said that baseline characteristics were “generally well balanced” between the nivolumab (n = 221) and placebo (n = 111) arms.

However, there were more patients with a PD-L1 tumor proportion score (TPS) of at least 1% among the patients given nivolumab, at 37% versus 29% in the placebo arm.

After a median follow-up of 17.1 months in the nivolumab arm and 14.2 months in the placebo group, overall survival was significantly longer with the active treatment, at 9.2 months versus 6.6 months with placebo (hazard ratio, 0.72; P = .018).

The proportion of patients alive at 12 months was 39.5% in the nivolumab group and 26.9% in patients given placebo. Investigator-assessed PFS was also significantly longer with nivolumab, at 3.0 months versus 1.8 months with placebo (HR, 0.61; P < .001).

The proportion of patients disease free at 12 months was 14.5% with active treatment versus 4.9% months with the placebo.

“The role for PD-L1 as a potential biomarker was assessed,” Dr. Fennell said, using the Dako 22C3 antibody, with 150 nivolumab and 84 placebo patients divided into those with a TPS <1% or ≥1%.

He noted that PD-L1 expression in the tumor “did not predict survival for patients in the CONFIRM trial,” with neither PD-L1 positive nor PD-L1 negative patients demonstrating a significant improvement in overall survival with nivolumab vs placebo.

“For histology, epithelioid mesothelioma patients benefited from nivolumab,” Dr. Fennell continued, with a hazard ratio for death of 0.71 versus placebo (P = .021). “However, for the nonepithelioid subgroup, in this immature survival analysis ... the P value was not significant,” but this was a small subgroup of patients (12% in both nivolumab and placebo groups).

The safety analysis revealed that the proportion of patients with any serious adverse events, of any grade or grade 3 or higher, was almost identical between the active and placebo arms, Dr. Fennel reported. There were five deaths (3.6%) related to a serious adverse event in the nivolumab arm and four (5.3%) in the placebo group.

This research was funded by the Stand Up to Cancer campaign for Cancer Research UK, supported by Cancer Research UK core funding at the Southampton Clinical Trials Unit, and investigator-initiated support from Bristol-Myers Squibb for free drug labeling and distribution and funding for RECIST reporting. Dr. Fennell reported relationships with Astex Therapeutics, AstraZeneca, Atara Biotherapeutics, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Clovis Oncology, Eli Lilly, Inventiva, Lab 21, Merck, and Roche. Dr. Hui reported relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Seagen.

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

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

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

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

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

Screening for lung cancer with low-dose computed tomography (LDCT) has thus far been targeted at individuals who smoke or have smoked, but the incidence of lung cancer has been found to be increasing among people who have never smoked, and they too should undergo screening, suggest researchers from Taiwan.

“Lung cancer in never-smokers is a global rising threat,” said lead researcher Pan-Chyr Yang, MD, PhD, chair professor at the National Taiwan University Hospital and academician of Academia Sinica, Taiwan.

In Taiwan, more than half of the cases of lung cancer occur in never-smokers; among female lung cancer patients, 93% are never-smokers.

The incidence of lung cancer – in particular, adenocarcinoma – is increasing in Taiwan, even though the prevalence of smoking has fallen dramatically in men in recent years and has remained low in women.

At the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021, Dr. Yang presented new results that suggest “LDCT screening for never-smokers with high risk may be feasible.”

The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) recruited over 12,000 individuals aged 55-70 years who had never smoked or had done so more than 15 years previously and had risk factors such as a family history of the disease or passive smoke exposure, or who had regularly been exposed to frying food.

Participants underwent LDCT after chest x-ray, followed by biopsy if necessary.

These procedures detected largely invasive lung cancer in 2.6% of participants. Tumors were of stage 0-I in 95% of cases.

The lung cancer detection rate of 2.6% in TALENT in never-smokers is higher than has been found in large studies of smokers, including the 1.1% rate recorded in the NLST study and the 0.9% seen in the NELSON study.

The key factor associated with increased prevalence of lung cancer was a first-degree family history of the disease, Dr. Yang reported.

Notably, having a sister with lung cancer increased the risk for the disease by 78%. Having an affected brother doubled the risk. An increase in the number of first-degree relatives with lung cancer also significantly increased the risk.
 

More research needed

The TALENT study “provides new, very original evidence on lung cancer risks, and therefore lung cancer screening eligibility could be redefined in Asia, or at least in East Asia,” said the discussant for the paper, Ugo Pastorino, MD, director of thoracic surgery at IRCCS Istituto Nazionale dei Tumori Foundation, Milan.

However, he said that “more research is needed on lung cancer biology in nonsmokers.”

There is currently no follow-up or mortality data, and given the proportion of patients who underwent invasive procedures, it could be that more than 40% of those procedures were carried out in individuals with benign disease, he cautioned.

On Twitter, Stephen V. Liu, MD, director of thoracic oncology at Georgetown University, Washington, said that although family history “emerges” from the study as a potential risk factor for lung cancer, “this analysis would be much more insightful with genomic analyses of these cancers.”

Devika Das, MD, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham, said that the study is “interesting,” given the rise of adenocarcinoma among never-smokers.

She agreed that further details and long-term outcomes are needed and said the key learning point was the need for a “robust” study of the biology of lung cancer in this population.

Lillian Leigh, an Australian lawyer and a lung cancer patient advocate, said the study “provides new evidence” on lung cancer risks.

“As an Asian never-smoker living with lung cancer, the TALENT trial results give me hope,” she said.
 

Details of TALENT findings

The TALENT study recruited individuals aged 55-70 years at 17 medical centers between February 2015 and July 2019.

Participants were required to be never-smokers or to have a smoking history of less than 10 pack-years and to have quit the habit more than 15 years previously.

They also had to have one of the following risk factors:

• Family history of lung cancer in up to third-degree relatives, in which case younger patients could be recruited.
• Environmental (passive) tobacco smoking history.
• Chronic lung disease, namely,  or .
• A cooking index ≥110, defined as 2/7 × the number of days of frying per week × the number of years cooking.
• Cooking without ventilation.

The participants underwent chest x-ray. If the x-ray proved negative, the team performed standard LDCT, examined blood and urine samples for lung cancer biomarkers, and administered standard questionnaires.

Participants who were found on LDCT to have solid or part-solid nodules greater than 6 mm in diameter or pure ground-glass nodules greater than 5 mm in diameter underwent biopsy or standard follow-up.

Individuals whose initial chest x-ray was positive underwent standard contrast-enhanced chest CT prior to biopsy or standard follow-up.

Of 13,207 individuals initially screened, 12,011 were enrolled. Of those, 73.8% were women. The mean age was 61.2 years, and 93.3% were never-smokers.

Among the participants, 46.4% had a first-degree family history of lung cancer; 3.0% had a second-degree family history; and 0.5% had a third-degree family history.

Environmental tobacco exposure was recorded in 83.2% of patients. Chronic lung disease was present in 9.8%; 36.7% had a cooking index ≥110; and 1.8 cooked without ventilation.

Dr. Yang said LDCT results were positive for 17.4% of patients, and 3.4% underwent invasive procedures.

Overall, lung cancer was detected in 313 participants (2.6%). Invasive lung cancer was detected in 255 (2.1%). Of those, 17.9% had multiple primary lung cancers.

Strikingly, 96.5% of the confirmed lung cancer cases were stage 0-I. The majority were stage IA, “which is higher than in other studies that have focused on heavy smokers,” Dr. Yang said. More than half of cases (58.5%) were invasive adenocarcinomas.

The prevalence of lung cancer was significantly higher among people who had a family history of the disease, at 3.2%, vs. 2.0% in those without, at a relative risk of 1.61 (P < .001).

The prevalence was higher still in individuals who had a first-degree family history of lung cancer, at 3.3%, giving a relative risk of 1.69 in comparison with those who did not have a family history (P < .001). The findings were nonsignificant for second- and third-degree relatives.

The relative risk increased even further when the first-degree relative who had a history of lung cancer was a sister, at 1.78 (P < .001), or a brother, at 2.00 (P < .001).

The relative risk was slightly lower if the patient’s relative was the mother, at 1.43 (P = .010), and was nonsignificant if the relative was the father (P = .077).

The risk for lung cancer also increased with an increase in the number of first-degree relatives with the disease, rising from 3.1% with one relative to 4.0% with two relatives, 6.7% with three relatives, and 9.1% with at least four relatives (P < .001). A similar pattern was seen for invasive lung cancer.

The other risk factors included in the study, such as environmental tobacco exposure, chronic lung disease, and cooking index, were not significantly associated with the prevalence of lung cancer.

No funding for the study has been disclosed. Dr. Yang has received honoraria from AstraZeneca, Boehringer Ingelheim, Pfizer, Merck, Eli Lilly, Roche, GlaxoSmithKline, and ONO Pharma and has served on the advisory board of OBI Pharma, CHO Pharma, and Lin BioScience. Dr. Pastorino has disclosed no relevant financial relationships.

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

Lung cancer experts have been rejoicing over new longer-term results that continue to show the combination of immunotherapy and chemotherapy doubles survival, compared with chemotherapy alone.

The results are from a 4-year follow-up of 160 patients with previously untreated stage IV non–small cell lung cancer (NSCLC) taking part in the KEYNOTE-189 trial of immunotherapy with pembrolizumab plus pemetrexed–platinum chemotherapy versus chemotherapy plus placebo.

After a median follow-up of 46.3 months, the median overall survival (OS) in the intention-to-treat population was 22.0 months with the combination versus 10.6 months with chemotherapy alone (hazard ratio, 0.60).

A similar pattern was seen for progression-free survival (PFS), with patients receiving the combination having a longer median PFS, at 9.0 months versus 4.9 months with chemotherapy alone (HR, 0.50).

“Stellar data,” Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust, Royal Tunbridge Wells, England, exclaimed on Twitter.

He described the results for the programmed death-ligand 1 (PD-L1) expression subgroups as “astonishing” and singled out the performance of the combination therapy in patients with very low (<1%) tumor PD-L1 expression, showing more than 23% of patients were alive at 3 years versus just over 5% in the group given chemotherapy alone.

Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence, Penn Medicine, Philadelphia, said the outcomes with the combination of chemotherapy and immunotherapy were “terrific.”

Sandip P. Patel, MD, medical oncologist, associate professor of medicine, University of California, San Diego, agreed that these long-term results were “very impressive.” However, he noted the “full effect” of chemotherapy plus immunotherapy has not “fully been captured in our overall cancer mortality statistics in the U.S. yet.”

The new results were presented at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Previous results from KEYNOTE-189 had already demonstrated that, after a median follow-up of 10.5 months, adding pembrolizumab to chemotherapy significantly improves both OS and PFS, compared with chemotherapy alone.

The latest results show that the combination “continued to provide overall survival and progression-free survival benefit” in extended follow-up, said study presenter Jhanelle Elaine Gray, MD, chair, department of thoracic oncology, Moffitt Cancer Center, Tampa.

The 3-year OS rate with pembrolizumab plus chemotherapy, compared with chemotherapy alone was 31.3% versus 17.4%, and the estimated 3-year PFS was 11.8% versus 1.3%.

Substantial improvements were even seen in patients with tumors that had a low level of PD-L1 expression (measured as the PD-L1 tumor proportion score [TPS]).

Dr. Gray highlighted the finding that the survival benefit with pembrolizumab plus chemotherapy was seen regardless of PD-L1 expression in the tumor, with a hazard ratio versus chemotherapy alone of 0.71 in patients with a TPS ≥ 50%, 0.66 in those with a TPS of 1%-49%, and 0.52 in patients with a TPS less than 1%. A similar pattern was seen with PFS, with a hazard ratio of 0.36 in patients with a TPS of at least 50%, 0.54 in those with a TPS of 1%-49%, and 0.68 in patients with a TPS less than 1%.

In addition, overall response rate and duration of response were also improved with combination therapy, regardless of tumor PD-L1 expression.

Among 56 patients who completed 35 cycles of pembrolizumab, the objective response rate was 87.5% (with 10.7% having a complete response and 76.8% a partial response).

At the data cutoff, 45 patients were alive, 28 did not have progressive disease, and seven had started a second course of pembrolizumab.

The side effect profile of the combination was “manageable,” Dr. Gray reported.

The combination arm was associated with more grade 3-5 treatment-related adverse events than the chemotherapy alone arm, at 52.1% versus 42.1%, and more grade 3-5 immune-related adverse events and infusion reactions, at 27.7% versus 13.4%.

Events leading to treatment discontinuation were also more common with pembrolizumab plus chemotherapy than chemotherapy, at 27.4% versus 9.9%.

The combination of pembrolizumab plus pemetrexed-platinum has already become “a standard-of-care therapy for patients with newly diagnosed metastatic nonsquamous NSCLC,” Dr. Gray commented.

The study was funded by Merck. Dr. Gray disclosed relationships with Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, and Merck.

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

Lung cancer experts have been rejoicing over new longer-term results that continue to show the combination of immunotherapy and chemotherapy doubles survival, compared with chemotherapy alone.

The results are from a 4-year follow-up of 160 patients with previously untreated stage IV non–small cell lung cancer (NSCLC) taking part in the KEYNOTE-189 trial of immunotherapy with pembrolizumab plus pemetrexed–platinum chemotherapy versus chemotherapy plus placebo.

After a median follow-up of 46.3 months, the median overall survival (OS) in the intention-to-treat population was 22.0 months with the combination versus 10.6 months with chemotherapy alone (hazard ratio, 0.60).

A similar pattern was seen for progression-free survival (PFS), with patients receiving the combination having a longer median PFS, at 9.0 months versus 4.9 months with chemotherapy alone (HR, 0.50).

“Stellar data,” Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust, Royal Tunbridge Wells, England, exclaimed on Twitter.

He described the results for the programmed death-ligand 1 (PD-L1) expression subgroups as “astonishing” and singled out the performance of the combination therapy in patients with very low (<1%) tumor PD-L1 expression, showing more than 23% of patients were alive at 3 years versus just over 5% in the group given chemotherapy alone.

Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence, Penn Medicine, Philadelphia, said the outcomes with the combination of chemotherapy and immunotherapy were “terrific.”

Sandip P. Patel, MD, medical oncologist, associate professor of medicine, University of California, San Diego, agreed that these long-term results were “very impressive.” However, he noted the “full effect” of chemotherapy plus immunotherapy has not “fully been captured in our overall cancer mortality statistics in the U.S. yet.”

The new results were presented at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Previous results from KEYNOTE-189 had already demonstrated that, after a median follow-up of 10.5 months, adding pembrolizumab to chemotherapy significantly improves both OS and PFS, compared with chemotherapy alone.

The latest results show that the combination “continued to provide overall survival and progression-free survival benefit” in extended follow-up, said study presenter Jhanelle Elaine Gray, MD, chair, department of thoracic oncology, Moffitt Cancer Center, Tampa.

The 3-year OS rate with pembrolizumab plus chemotherapy, compared with chemotherapy alone was 31.3% versus 17.4%, and the estimated 3-year PFS was 11.8% versus 1.3%.

Substantial improvements were even seen in patients with tumors that had a low level of PD-L1 expression (measured as the PD-L1 tumor proportion score [TPS]).

Dr. Gray highlighted the finding that the survival benefit with pembrolizumab plus chemotherapy was seen regardless of PD-L1 expression in the tumor, with a hazard ratio versus chemotherapy alone of 0.71 in patients with a TPS ≥ 50%, 0.66 in those with a TPS of 1%-49%, and 0.52 in patients with a TPS less than 1%. A similar pattern was seen with PFS, with a hazard ratio of 0.36 in patients with a TPS of at least 50%, 0.54 in those with a TPS of 1%-49%, and 0.68 in patients with a TPS less than 1%.

In addition, overall response rate and duration of response were also improved with combination therapy, regardless of tumor PD-L1 expression.

Among 56 patients who completed 35 cycles of pembrolizumab, the objective response rate was 87.5% (with 10.7% having a complete response and 76.8% a partial response).

At the data cutoff, 45 patients were alive, 28 did not have progressive disease, and seven had started a second course of pembrolizumab.

The side effect profile of the combination was “manageable,” Dr. Gray reported.

The combination arm was associated with more grade 3-5 treatment-related adverse events than the chemotherapy alone arm, at 52.1% versus 42.1%, and more grade 3-5 immune-related adverse events and infusion reactions, at 27.7% versus 13.4%.

Events leading to treatment discontinuation were also more common with pembrolizumab plus chemotherapy than chemotherapy, at 27.4% versus 9.9%.

The combination of pembrolizumab plus pemetrexed-platinum has already become “a standard-of-care therapy for patients with newly diagnosed metastatic nonsquamous NSCLC,” Dr. Gray commented.

The study was funded by Merck. Dr. Gray disclosed relationships with Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, and Merck.

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

Lung cancer experts have been rejoicing over new longer-term results that continue to show the combination of immunotherapy and chemotherapy doubles survival, compared with chemotherapy alone.

The results are from a 4-year follow-up of 160 patients with previously untreated stage IV non–small cell lung cancer (NSCLC) taking part in the KEYNOTE-189 trial of immunotherapy with pembrolizumab plus pemetrexed–platinum chemotherapy versus chemotherapy plus placebo.

After a median follow-up of 46.3 months, the median overall survival (OS) in the intention-to-treat population was 22.0 months with the combination versus 10.6 months with chemotherapy alone (hazard ratio, 0.60).

A similar pattern was seen for progression-free survival (PFS), with patients receiving the combination having a longer median PFS, at 9.0 months versus 4.9 months with chemotherapy alone (HR, 0.50).

“Stellar data,” Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust, Royal Tunbridge Wells, England, exclaimed on Twitter.

He described the results for the programmed death-ligand 1 (PD-L1) expression subgroups as “astonishing” and singled out the performance of the combination therapy in patients with very low (<1%) tumor PD-L1 expression, showing more than 23% of patients were alive at 3 years versus just over 5% in the group given chemotherapy alone.

Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence, Penn Medicine, Philadelphia, said the outcomes with the combination of chemotherapy and immunotherapy were “terrific.”

Sandip P. Patel, MD, medical oncologist, associate professor of medicine, University of California, San Diego, agreed that these long-term results were “very impressive.” However, he noted the “full effect” of chemotherapy plus immunotherapy has not “fully been captured in our overall cancer mortality statistics in the U.S. yet.”

The new results were presented at the 2020 World Conference on Lung Cancer, which was rescheduled for January 2021.

Previous results from KEYNOTE-189 had already demonstrated that, after a median follow-up of 10.5 months, adding pembrolizumab to chemotherapy significantly improves both OS and PFS, compared with chemotherapy alone.

The latest results show that the combination “continued to provide overall survival and progression-free survival benefit” in extended follow-up, said study presenter Jhanelle Elaine Gray, MD, chair, department of thoracic oncology, Moffitt Cancer Center, Tampa.

The 3-year OS rate with pembrolizumab plus chemotherapy, compared with chemotherapy alone was 31.3% versus 17.4%, and the estimated 3-year PFS was 11.8% versus 1.3%.

Substantial improvements were even seen in patients with tumors that had a low level of PD-L1 expression (measured as the PD-L1 tumor proportion score [TPS]).

Dr. Gray highlighted the finding that the survival benefit with pembrolizumab plus chemotherapy was seen regardless of PD-L1 expression in the tumor, with a hazard ratio versus chemotherapy alone of 0.71 in patients with a TPS ≥ 50%, 0.66 in those with a TPS of 1%-49%, and 0.52 in patients with a TPS less than 1%. A similar pattern was seen with PFS, with a hazard ratio of 0.36 in patients with a TPS of at least 50%, 0.54 in those with a TPS of 1%-49%, and 0.68 in patients with a TPS less than 1%.

In addition, overall response rate and duration of response were also improved with combination therapy, regardless of tumor PD-L1 expression.

Among 56 patients who completed 35 cycles of pembrolizumab, the objective response rate was 87.5% (with 10.7% having a complete response and 76.8% a partial response).

At the data cutoff, 45 patients were alive, 28 did not have progressive disease, and seven had started a second course of pembrolizumab.

The side effect profile of the combination was “manageable,” Dr. Gray reported.

The combination arm was associated with more grade 3-5 treatment-related adverse events than the chemotherapy alone arm, at 52.1% versus 42.1%, and more grade 3-5 immune-related adverse events and infusion reactions, at 27.7% versus 13.4%.

Events leading to treatment discontinuation were also more common with pembrolizumab plus chemotherapy than chemotherapy, at 27.4% versus 9.9%.

The combination of pembrolizumab plus pemetrexed-platinum has already become “a standard-of-care therapy for patients with newly diagnosed metastatic nonsquamous NSCLC,” Dr. Gray commented.

The study was funded by Merck. Dr. Gray disclosed relationships with Array, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, and Merck.

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

Cardiovascular disease and related risk factors can be common among male breast cancer patients, suggests a small study in this rare malignancy.

Among 24 male breast cancer patients evaluated over a decade in the Washington area, 88% were obese or overweight, 58% had hypertension, and 54% had hyperlipidemia.

Tachyarrhythmia existed in 8% of the men before cancer treatment and developed in 13% during treatment.

Two patients had preexisting heart failure, two patients developed the disease after treatment, and another two patients experienced a decline in left ventricular ejection fraction during the course of their cancer treatment.

“Our hope is that treating male breast cancer patients becomes a multidisciplinary approach where oncologists recruit their cardio-oncologist counterparts to mitigate cardiovascular risk factors, so patients live a long and healthy life after cancer treatment,” said Michael Ibrahim, one of the study authors and a 4th-year medical student at Georgetown University in Washington.

The data were presented Jan. 25 as part of the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient virtual course, which is hosting live sessions Feb. 5-6.

Although the association between cardiovascular disease and breast cancer is well documented in female breast cancer patients, there is little evidence in their male counterparts, especially African Americans, Mr. Ibrahim noted.

To provide some context, Mr. Ibrahim highlighted a 2018 report in nearly 3,500 female breast cancer patients, ages 40-79, in whom 52% were obese/overweight, 35% had hypertension, and 28% had hyperlipidemia.

Diabetes was present in 7.5% of the women, which was roughly equivalent to the 8% found among the men, Mr. Ibrahim said. The men were of similar age (38-79 years), with 42% being African American, 29% White, 4% Hispanic, and 25% another ethnicity.

Importantly, half of the men had a family history of breast cancer, and two were positive for a mutation in the BRCA gene.

A 2017 in-depth review of male breast cancer cites advancing age, hormonal imbalance, radiation exposure, and family history of breast cancer as key risk factors for the development of the disease, but the “most relevant risk factor” is a mutation in the BRCA2 gene.

Male breast cancer accounts for less than 1% of all breast cancers, but the incidence is rising and, in some patient groups, reaching 15% over their lifetimes, the paper notes. Additionally, these patients are at special risk for developing a second cancer.

Remarkably, 25% of men in the D.C. cohort were diagnosed with a second primary malignancy, 13% a third primary cancer, and 4% a fourth primary cancer, Mr. Ibrahim reported. “This goes to show that male breast cancer patients should routinely undergo cancer screening,” he said.

The initial diagnosis was invasive ductal carcinoma in 79% of the men, with the remaining ductal carcinoma in situ. All patients underwent mastectomy, 17% had anthracycline chemotherapy, 8% received HER2-targeted therapy, 16% had radiation, and 71% received hormone therapy.

In terms of cardiovascular management, statins were the most prescribed medication (46%), followed by antiplatelet therapy (42%) and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (38%).

An implantable cardioverter defibrillator/pacemaker was the most common intervention (16%), followed by bypass surgery in 8% and coronary angioplasty in 4%.

Mr. Ibrahim noted that the study was limited by the small sample size and that further research is needed to understand the risk of preexisting cardiovascular disease on long-term outcomes as well as the cardiotoxic effects of chemoradiation in male breast cancer patients.

In a statement, Mr. Ibrahim reiterated the need for a multidisciplinary cancer care team to evaluate patients’ cardiovascular risk prior to and through cancer treatment.

“On a more personal level, cancer patients are already surprised by their cancer diagnosis,” he added. “Similar to the pretreatment consultation with radiation oncology, breast surgery, and medical oncology, an upfront cardiovascular risk assessment provides greater comfort and further minimizes psychological surprise with cardiovascular complications going into cancer treatment.”

The authors have disclosed no relevant financial relationships.

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

Cardiovascular disease and related risk factors can be common among male breast cancer patients, suggests a small study in this rare malignancy.

Among 24 male breast cancer patients evaluated over a decade in the Washington area, 88% were obese or overweight, 58% had hypertension, and 54% had hyperlipidemia.

Tachyarrhythmia existed in 8% of the men before cancer treatment and developed in 13% during treatment.

Two patients had preexisting heart failure, two patients developed the disease after treatment, and another two patients experienced a decline in left ventricular ejection fraction during the course of their cancer treatment.

“Our hope is that treating male breast cancer patients becomes a multidisciplinary approach where oncologists recruit their cardio-oncologist counterparts to mitigate cardiovascular risk factors, so patients live a long and healthy life after cancer treatment,” said Michael Ibrahim, one of the study authors and a 4th-year medical student at Georgetown University in Washington.

The data were presented Jan. 25 as part of the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient virtual course, which is hosting live sessions Feb. 5-6.

Although the association between cardiovascular disease and breast cancer is well documented in female breast cancer patients, there is little evidence in their male counterparts, especially African Americans, Mr. Ibrahim noted.

To provide some context, Mr. Ibrahim highlighted a 2018 report in nearly 3,500 female breast cancer patients, ages 40-79, in whom 52% were obese/overweight, 35% had hypertension, and 28% had hyperlipidemia.

Diabetes was present in 7.5% of the women, which was roughly equivalent to the 8% found among the men, Mr. Ibrahim said. The men were of similar age (38-79 years), with 42% being African American, 29% White, 4% Hispanic, and 25% another ethnicity.

Importantly, half of the men had a family history of breast cancer, and two were positive for a mutation in the BRCA gene.

A 2017 in-depth review of male breast cancer cites advancing age, hormonal imbalance, radiation exposure, and family history of breast cancer as key risk factors for the development of the disease, but the “most relevant risk factor” is a mutation in the BRCA2 gene.

Male breast cancer accounts for less than 1% of all breast cancers, but the incidence is rising and, in some patient groups, reaching 15% over their lifetimes, the paper notes. Additionally, these patients are at special risk for developing a second cancer.

Remarkably, 25% of men in the D.C. cohort were diagnosed with a second primary malignancy, 13% a third primary cancer, and 4% a fourth primary cancer, Mr. Ibrahim reported. “This goes to show that male breast cancer patients should routinely undergo cancer screening,” he said.

The initial diagnosis was invasive ductal carcinoma in 79% of the men, with the remaining ductal carcinoma in situ. All patients underwent mastectomy, 17% had anthracycline chemotherapy, 8% received HER2-targeted therapy, 16% had radiation, and 71% received hormone therapy.

In terms of cardiovascular management, statins were the most prescribed medication (46%), followed by antiplatelet therapy (42%) and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (38%).

An implantable cardioverter defibrillator/pacemaker was the most common intervention (16%), followed by bypass surgery in 8% and coronary angioplasty in 4%.

Mr. Ibrahim noted that the study was limited by the small sample size and that further research is needed to understand the risk of preexisting cardiovascular disease on long-term outcomes as well as the cardiotoxic effects of chemoradiation in male breast cancer patients.

In a statement, Mr. Ibrahim reiterated the need for a multidisciplinary cancer care team to evaluate patients’ cardiovascular risk prior to and through cancer treatment.

“On a more personal level, cancer patients are already surprised by their cancer diagnosis,” he added. “Similar to the pretreatment consultation with radiation oncology, breast surgery, and medical oncology, an upfront cardiovascular risk assessment provides greater comfort and further minimizes psychological surprise with cardiovascular complications going into cancer treatment.”

The authors have disclosed no relevant financial relationships.

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

Cardiovascular disease and related risk factors can be common among male breast cancer patients, suggests a small study in this rare malignancy.

Among 24 male breast cancer patients evaluated over a decade in the Washington area, 88% were obese or overweight, 58% had hypertension, and 54% had hyperlipidemia.

Tachyarrhythmia existed in 8% of the men before cancer treatment and developed in 13% during treatment.

Two patients had preexisting heart failure, two patients developed the disease after treatment, and another two patients experienced a decline in left ventricular ejection fraction during the course of their cancer treatment.

“Our hope is that treating male breast cancer patients becomes a multidisciplinary approach where oncologists recruit their cardio-oncologist counterparts to mitigate cardiovascular risk factors, so patients live a long and healthy life after cancer treatment,” said Michael Ibrahim, one of the study authors and a 4th-year medical student at Georgetown University in Washington.

The data were presented Jan. 25 as part of the American College of Cardiology’s Advancing the Cardiovascular Care of the Oncology Patient virtual course, which is hosting live sessions Feb. 5-6.

Although the association between cardiovascular disease and breast cancer is well documented in female breast cancer patients, there is little evidence in their male counterparts, especially African Americans, Mr. Ibrahim noted.

To provide some context, Mr. Ibrahim highlighted a 2018 report in nearly 3,500 female breast cancer patients, ages 40-79, in whom 52% were obese/overweight, 35% had hypertension, and 28% had hyperlipidemia.

Diabetes was present in 7.5% of the women, which was roughly equivalent to the 8% found among the men, Mr. Ibrahim said. The men were of similar age (38-79 years), with 42% being African American, 29% White, 4% Hispanic, and 25% another ethnicity.

Importantly, half of the men had a family history of breast cancer, and two were positive for a mutation in the BRCA gene.

A 2017 in-depth review of male breast cancer cites advancing age, hormonal imbalance, radiation exposure, and family history of breast cancer as key risk factors for the development of the disease, but the “most relevant risk factor” is a mutation in the BRCA2 gene.

Male breast cancer accounts for less than 1% of all breast cancers, but the incidence is rising and, in some patient groups, reaching 15% over their lifetimes, the paper notes. Additionally, these patients are at special risk for developing a second cancer.

Remarkably, 25% of men in the D.C. cohort were diagnosed with a second primary malignancy, 13% a third primary cancer, and 4% a fourth primary cancer, Mr. Ibrahim reported. “This goes to show that male breast cancer patients should routinely undergo cancer screening,” he said.

The initial diagnosis was invasive ductal carcinoma in 79% of the men, with the remaining ductal carcinoma in situ. All patients underwent mastectomy, 17% had anthracycline chemotherapy, 8% received HER2-targeted therapy, 16% had radiation, and 71% received hormone therapy.

In terms of cardiovascular management, statins were the most prescribed medication (46%), followed by antiplatelet therapy (42%) and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (38%).

An implantable cardioverter defibrillator/pacemaker was the most common intervention (16%), followed by bypass surgery in 8% and coronary angioplasty in 4%.

Mr. Ibrahim noted that the study was limited by the small sample size and that further research is needed to understand the risk of preexisting cardiovascular disease on long-term outcomes as well as the cardiotoxic effects of chemoradiation in male breast cancer patients.

In a statement, Mr. Ibrahim reiterated the need for a multidisciplinary cancer care team to evaluate patients’ cardiovascular risk prior to and through cancer treatment.

“On a more personal level, cancer patients are already surprised by their cancer diagnosis,” he added. “Similar to the pretreatment consultation with radiation oncology, breast surgery, and medical oncology, an upfront cardiovascular risk assessment provides greater comfort and further minimizes psychological surprise with cardiovascular complications going into cancer treatment.”

The authors have disclosed no relevant financial relationships.

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