AVAHO

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.

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

A new study links the COVID-19 pandemic to decreased lung cancer diagnoses, changes in disease severity, and worsened outcomes for patients with lung cancer.

The two-center study showed a 38% decrease in new lung cancer diagnoses during the pandemic. Patients diagnosed with non–small cell lung cancer (NSCLC) during the pandemic had more severe disease than patients diagnosed prepandemic, but cases of SCLC were not more severe during the pandemic. Still, the 30-day mortality rate nearly doubled for both NSCLC and SCLC patients during the pandemic.

“The prioritization of the health care system towards COVID-19 patients has led to drastic changes in cancer management that could interfere with the initial diagnosis of lung cancer, resulting in delayed treatment and worse outcomes,” said Roxana Reyes, MD, of Hospital Clínic de Barcelona. “Delay of cancer treatment is associated with increased mortality.”

Dr. Reyes and colleagues conducted a retrospective study of the impact of COVID-19 on the incidence of new lung cancer cases, disease severity, and clinical outcomes. Dr. Reyes reported the group’s findings at the 2020 World Conference on Lung Cancer (Abstract 3700), which was rescheduled for January 2021.
 

Study details

Dr. Reyes and colleagues compared data from two tertiary hospitals in Spain in the first 6 months of 2020 with data from the same period in 2019. Spain was one of the countries most affected by COVID-19 during the first wave of the pandemic.

The study’s primary endpoint was differences by period in the number of new lung cancer cases and disease severity. A secondary endpoint was 30-day mortality rate by period and histology.

The study included 162 patients newly diagnosed with lung cancer – 100 diagnosed before the pandemic began and 62 diagnosed during the pandemic. Overall, 68% of patients had NSCLC, and 32% had SCLC.

Baseline characteristics were similar between the prepandemic and pandemic groups, except for the proportion of nonsmokers. Twice as many patients diagnosed during the pandemic were nonsmokers (16% vs. 8%).
 

Differences by time period and subtype

During the pandemic, there was a 38% reduction in all lung cancer diagnoses, a 36% reduction in NSCLC diagnoses, and a 42% reduction in SCLC diagnoses.

Respiratory symptoms were more common during the pandemic for both NSCLC (30% vs. 23%) and SCLC (32% vs. 24%).

Cases of NSCLC diagnosed during the pandemic were more severe, but SCLC cases were not.

In the NSCLC cohort, symptomatic disease was more common during the pandemic (74% vs. 63%), as were advanced disease (58% vs. 46%), more than two metastatic sites (16% vs. 12%), oncologic emergencies (7% vs. 3%), hospitalization (21% vs. 18%), and death during hospitalization (44% vs. 17%).

For SCLC, symptomatic disease was less common during the pandemic (74% vs. 79%), as were advanced disease (52% vs. 67%), more than two metastatic sites (26% vs. 36%), oncologic emergencies (5% vs. 12%), hospitalization (21% vs. 33%), and death during hospitalization (0% vs. 18%).

Nevertheless, the 30-day mortality rate almost doubled during the pandemic for both NSCLC (49% vs. 25%) and SCLC (32% vs. 18%).

For both subtypes together, the median overall survival was 6.7 months during the pandemic and 7.9 months before the pandemic.
 

Implications and next steps

“In our descriptive study, lung cancer diagnosis is being affected during the COVID-19 pandemic,” Dr. Reyes said. “Fewer new lung cancer cases were diagnosed during COVID-19.”

Some patients with acute respiratory infections who tested negative for COVID-19 during the first 6 months of the pandemic may have had undiagnosed lung cancer, noted Matthew Peters, MD, of Concord Repatriation General Hospital and Macquarie University Hospital, both in Sydney, who was not involved in this study.

“They receive a negative result and think their problem is reduced but wonder why they still have a cough,” Dr. Peters said. “The various lockdowns and social distancing reduced the diagnosis of respiratory viral illnesses that often result in an accidental diagnosis of lung cancer. As time goes by, we will recapture harvesting of accidental diagnosis of lung cancer and provide curative treatments.”

Dr. Reyes emphasized that strategies for maintaining cancer diagnoses need to be implemented during the pandemic. She also noted that this study is ongoing, with the goal of assessing the long-term impact of COVID-19.

Dr. Reyes disclosed relationships with Roche, Bristol-Myers Squibb, and Merck Sharp & Dohme. She did not disclose funding for this study. Dr. Peters disclosed relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche, and Takeda.

The use of low-dose aspirin among older people shows no effect in reducing the incidence of certain cancer types. However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.

“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open. 

“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.

In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.

“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.

“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
 

Aspirin/cancer research in older people lacking

With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.

However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.

To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.

The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.

Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.

The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.

However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.

A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.

“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
 

Mechanism speculation focuses on COX-2 pathway

Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.  

In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.

“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.

The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.

Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.

“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”

Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.

“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”

The study authors and Dr. McNeil disclosed no relevant financial relationships.

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

The use of low-dose aspirin among older people shows no effect in reducing the incidence of certain cancer types. However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.

“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open. 

“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.

In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.

“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.

“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
 

Aspirin/cancer research in older people lacking

With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.

However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.

To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.

The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.

Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.

The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.

However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.

A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.

“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
 

Mechanism speculation focuses on COX-2 pathway

Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.  

In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.

“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.

The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.

Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.

“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”

Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.

“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”

The study authors and Dr. McNeil disclosed no relevant financial relationships.

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

The use of low-dose aspirin among older people shows no effect in reducing the incidence of certain cancer types. However, the treatment – particularly with frequency of at least three times a week – is associated with reductions in mortality in bladder cancer and breast cancer, new observational research shows.

“The results presented here add to the accumulating evidence that aspirin may improve survival for some cancers,” the authors write in their cohort study that uses data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The new research was published online Jan. 15 in JAMA Network Open. 

“Although prior research has been most heavily concentrated in gastrointestinal cancers, our analysis extends the advantages associated with aspirin use to other cancers, such as bladder and breast cancers,” they explained.

In commenting on the study, John J. McNeil, MBBS, PhD, head of the department of epidemiology and preventive medicine at Monash University in Melbourne, said the findings, though intriguing, are not necessarily conclusive.

“The data was derived from a very large and well-conducted study,” Dr. McNeil, who has led other research on aspirin use and the elderly, said in an interview.

“But these conclusions were drawn from the observational component of the study and therefore potentially confounded by other characteristics that differentiate aspirin users from nonusers.”
 

Aspirin/cancer research in older people lacking

With well-known reports of decreased risks of heart disease, stroke, cancer – particularly gastrointestinal cancers – and all-cause mortality, as many as 25%-50% of adults in the U.S. report taking aspirin daily or every other day.

However, evidence of the benefits relating to cancer, specifically in older people, has been inconsistent, with one recent notable study, the randomized, double-blind ASPREE trial, showing no effect of aspirin on cancer incidence, but a higher mortality rate in elderly patients randomly assigned to aspirin for primary prevention.

To further investigate the effects in older patients, first author Holli A. Loomans-Kropp, PhD, and colleagues with the National Cancer Institute evaluated data on patients who were either 65 years or older at baseline or who had reached aged 65 during follow-up in the PLCO Cancer Screening Trial, which had enrollment from 1993 to 2001.

The authors identified 139,896 individuals with a mean age at baseline of 66.4 years; about half were women and 88.5% were non-Hispanic White.

Follow-up took place until the time of death, December 2014 for those who consented to follow-up, or December 2009 for those who refused consent to follow-up. The authors reported that there were 32,580 incident cancers, including 5.4% bladder, 14% breast, 1% esophageal, 1.2% gastric, 2.7% pancreatic, and 2.2% uterine cancers.

The study showed no association between aspirin use and the incidence of any of the cancer types included in the study among those over age 65.

However, further multivariate analysis of survival showed that, with follow-up adjusted to until the time of death, Dec. 31, 2015, or earlier refusal to consent, the use of aspirin at least three times per week was associated with reduced mortality in those with bladder (hazard ratio, 0.67) and breast (HR, 0.75) cancers, whereas no significant associations were observed with esophageal, gastric, pancreatic, or uterine cancer.

A similar association of any aspirin use (less than three times per week) with bladder (HR, 0.75) and breast (HR, 0.79) cancer survival was observed, the authors noted.

“These results may indicate that, for some cancer types, any aspirin use may be advantageous; however, greater benefit may be observed with increased frequency of use,” the authors wrote.
 

Mechanism speculation focuses on COX-2 pathway

Theories of the mechanisms behind a potential benefit of aspirin for those with bladder cancer include that urothelial cancer has increased RNA and protein expression of cyclooxygenase-2 (COX-2) and urinary prostaglandin E2, “suggesting up-regulation of the COX-2 pathway during cancer progression,” the authors wrote.  

In breast cancer, a similar elevated expression of COX-2 has been shown to predict disease outcomes, including progression and decreased survival.

“This may be partly due to the mechanistic interplay between angiogenesis, cell proliferation, apoptosis, and inflammatory processes,” the authors noted.

The study isn’t the first to show a benefit specifically with bladder cancer; other studies include recent research (J Urol. 2018 Nov;200[5]:1014-21) showing that daily aspirin use among patients with bladder cancer was associated with increased 5-year survival following radical cystectomy, the authors noted.

Dr. McNeil noted that the new findings from the U.S. researchers, particularly regarding bladder cancer, are of interest. “The reduction in mortality from breast cancer is modest, but the reduction in mortality from bladder cancer was more impressive,” he said.

“However, given the fact that this finding is observational data and was a sole finding among multiple comparisons, it must be seen as suggestive rather than proven.”

Regarding possible mechanisms, Dr. McNeil added that, like the bulk of the prior research, many questions remain.

“There have been many suggestions about ways that aspirin might work at a molecular and cellular level, but no firm consensus has been reached.”

The study authors and Dr. McNeil disclosed no relevant financial relationships.

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

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on Jan. 20 in the New England Journal of Medicine.

The two articles are “extraordinary” for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, Calif., and Medscape editor in chief.

“Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years,” commented the lead investigator of one of the studies, Fergus Couch, PhD, a pathologist at the Mayo Clinic, Rochester, Minn.

“[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease ... when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high risk,” he said.

In both studies, mutations or variants in eight genes – BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 – were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, noted Steven Narod, MD, from the Women’s College Research Institute, Toronto, in an accompanying editorial.

“What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations,” he wrote. Currently, these two are “clumped in with ‘other genes.’ ... Most of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation.”

The new findings may lead to new risk management strategies, he suggested. “Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for antiestrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors,” he wrote.

Dr. Narod observed that, for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons.

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. “All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately – it saves lives,” Dr. Taylor emphasized.

However, “unaffected people with no family history do not need genetic testing at this time,” he said in an interview.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Dr. Taylor said, “It’s surprisingly easy.”

Every genetic testing company provides genetic counselors to guide patients through next steps, Dr. Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Dr. Taylor said these are very useful guidelines for virtually all mutations identified thus far.

“This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway,” Dr. Taylor said. “It confirms that what we think is right is right – and that matters,.”
 

CARRIERS consortium findings

The study led by Dr. Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they added. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators stated.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they added.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 years among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51D increased the risk for estrogen receptor (ER)–negative breast cancer as well as triple-negative breast cancer, the authors noted, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

“These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer,” the CARRIERS authors observed.

“The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counseling of women with breast cancer who do not meet high-risk selection criteria,” they suggested.
 

Similar findings in second study

The second study was conducted by the Breast Cancer Association Consortium under lead author Leila Dorling, PhD, University of Cambridge (England). This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

“Protein-truncating variants in five genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a significant risk of breast cancer overall (P < .0001),” the BCAC members reported. “For these genes, odds ratios ranged from 2.10 to 10.57.”

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors noted. Again, the risk for ER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes – CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL – and overall breast cancer risk, with the clearest evidence being for CHEK2.

“The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category,” Dr. Dorling and colleagues reaffirmed.

“These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines,” the authors suggested.

The CARRIERS study was supported by the National Institutes of Health. The study by Dr. Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Dr. Narod disclosed no relevant financial relationships.

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

The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.

Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.

Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”

However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.

In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.

“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.

The study was published online Dec. 1 in The Breast.

“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.

Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?

No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”

The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.

For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.

Why is there such a contrast between early- and late-stage disease?

“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.

“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.

But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.

That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”

Dr. Ligibel summarized as follows:

“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
 

More study details

The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.

A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m²), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).

A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.

Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).

As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.

“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”

The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.

The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.

Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.

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

The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.

Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.

Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”

However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.

In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.

“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.

The study was published online Dec. 1 in The Breast.

“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.

Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?

No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”

The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.

For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.

Why is there such a contrast between early- and late-stage disease?

“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.

“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.

But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.

That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”

Dr. Ligibel summarized as follows:

“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
 

More study details

The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.

A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m²), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).

A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.

Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).

As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.

“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”

The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.

The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.

Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.

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

The relationship between obesity and overweight and breast cancer has some elements of mystery. But this is not one of them: in metastatic breast cancer (MBC), excess body weight does not negatively influence outcomes.

Multiple small studies have demonstrated this point, and now, for the first time, a large multicenter cohort analysis indicates the same.

Using medical records from 18 French comprehensive cancer centers, investigators reviewed body mass index (BMI) and overall survival (OS) data for nearly 13,000 women. The median OS was 47.4 months, and the median follow-up was about the same length of time. The team reports that obesity and overweight “were clearly not associated with prognosis.”

However, underweight was independently associated with worse OS (median, 33 months; hazard ratio, 1.14; 95% confidence interval, 1.02-1.27), report Khalil Saleh, MD, of Gustave Roussy in Villejuif, France, and colleagues.

In short, obesity or overweight had no effect on the primary outcome of OS, but underweight did.

“Underweight should be the subject of clinical attention at the time of diagnosis of MBC, and specific management should be implemented,” said study author Elise Deluche, MD, of CHU de Limoges, in an email to this news organization.

The study was published online Dec. 1 in The Breast.

“It’s really wonderful to have such a large cohort to look at this question,” said Jennifer Ligibel, MD, of the Dana-Farber Cancer Institute, Boston, who was asked for comment.

Is this another case of obesity paradox in cancer (as in renal cell carcinoma and melanoma, where excess weight is tied to better cancer-specific survival)?

No, said Dr. Ligibel: “There’s no hint at all [in this study] that people with obesity and overweight did better. … They just didn’t have worse outcomes.”

The study authors point out that the opposite is true in early-stage breast cancer. In this patient population, excess weight is associated with worse outcomes.

For example, in a 2014 meta-analysis of 82 follow-up studies in early-stage disease, obesity was associated with higher total mortality (relative risk, 1.41) and breast cancer–specific mortality (RR, 1.35) as compared to normal weight.

Why is there such a contrast between early- and late-stage disease?

“I don’t think we know exactly,” answered Dr. Ligibel. “It may be that, with breast cancer, as disease progresses, the pathways through which lifestyle may impact breast cancer may become less important.

“Obesity and overweight are associated with cancer risk in general,” said Dr. Ligibel, citing more than a dozen malignancies, including breast cancer.

But there is also an age element. Overweight or obesity is an independent predictor of breast cancer risk in postmenopausal women, but in premenopausal women, it appears to be protective. “Historically, there has been a lower risk of hormone receptor–positive breast cancer in women with obesity at younger ages that we don’t completely understand,” Dr. Ligibel noted.

That age-based difference is a conundrum, said Dr. Ligibel: “People have been trying to figure that out for a long time.”

Dr. Ligibel summarized as follows:

“There is a clear relationship between obesity and the risk of developing breast cancer; there is a clear relationship in early breast cancer that obesity is related to an increased risk of occurrence and mortality. What we are seeing from this study is that, by the time you get to metastatic breast cancer, body weight does not seem to play as important a role.”
 

More study details

The findings come from the French National Epidemiological Strategy and Medical Economics–Metastatic Breast Cancer observational cohort, which includes 22,000-plus consecutive patients who were newly diagnosed with metastatic disease between 2008 and 2016.

A total of 12,999 women for whom BMI data were available when they were diagnosed with metastatic breast cancer were selected for analysis. They were divided into four groups, according to World Health Organization classification: underweight (BMI <18.5 kg/m²), normal weight (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0).

A total of 20% of women were obese, which is a much lower percentage than the 40%-50% that would be expected in a comparable American cohort, said Dr. Ligibel. Also, 5% of the French cohort was underweight.

Multivariate Cox analyses were carried out for OS and for first-line progression-free survival (PFS).

As noted above, underweight was independently associated with a worse OS. It was also tied to worse first-line PFS (HR, 1.11; 95% CI, 1.01-1.22). Overweight or obesity had no effect.

“Patients with a low BMI had more visceral metastases and a greater number of metastatic sites,” pointed out study author Dr. Deluche. “We attribute the fat loss in patients with metastatic breast cancer to aggressive tumor behavior with a higher energy requirement.”

The study authors also observe that in early-stage breast cancer, underweight is not associated with overall or breast cancer–specific survival. “Underweight at metastatic diagnosis seems to have a different significance and impact,” they write. The French team also observes that, in other cancers, underweight is also an adverse prognostic factor and has been associated with a higher risk for death.

The study authors acknowledge that BMI has limitations as a measure of body type. “BMI alone cannot estimate a woman’s muscle mass and adiposity,” they observe. The suggestion is that, among women with a similar BMI, some might be muscular, whereas others might have more body fat.

Multiple study authors report financial ties to industry, including pharmaceutical companies with drugs used in breast cancer. The database used in the study receives financial support from AstraZeneca, Daiichi Sankyo, Eisai, MSD, Pfizer, and Roche. Dr. Ligibel reports no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

Dramatic changes in the use of radiotherapy for cancer were seen during the first wave of the COVID-19 pandemic in England. Some radiotherapy regimens were shortened, but others were intensified, suggesting that they were being used as a replacement for surgery.

The findings come from an analysis of National Health Service data in England, which also indicated that overall there was a reduction in the amount of radiotherapy delivered.

“Radiotherapy is a very important treatment option for cancer, and our study shows that, across the English NHS, there was a rapid shift in how radiotherapy was used,” said lead author Katie Spencer, PhD, faculty of medicine and health, University of Leeds (England).

“It is impressive to see that the data closely follow the guidelines published at the start of the pandemic,” she said. For instance, for patients with breast and colorectal cancers, treatment regimens were shorter and more intensive, whereas for patients with prostate cancer, treatments were delayed to reduce exposure to COVID-19.

“In other cases, such as head and neck cancers and anal cancers, we saw that the number of radiotherapy treatments hardly changed during the first wave. This was really reassuring, as we know that it is vital that these treatments are not delayed,” Dr. Spencer added.

The study was published online in The Lancet Oncology on Jan. 22 (doi: 10.1016/S1470-2045[20]30743-9).

Researchers examined data from the National Radiotherapy Dataset on all radiotherapy delivered for cancer in the NHS in England between Feb. 4, 2019, and June 28, 2020.

On interrupted time-series analysis, the introduction of lockdown in response to the COVID-19 pandemic was associated with a significant reduction in both radiotherapy courses and attendances (P < .0001).

Overall, the team estimated that there were 3,263 fewer radiotherapy treatment courses and 119,050 fewer attendances than would have taken place had the pandemic not occurred.

The largest reduction in treatment courses was seen for prostate cancer, with a 77% reduction in April 2020 in comparison with April 2019, and in nonmelanoma skin cancer, for which there was a decrease of 72.4% over the same period.

There were, however, marked increases in the number of radiotherapy courses given for some disorders in April 2020 in comparison with April 2019. Radiotherapy for bladder cancer increased by 64.2%; for esophageal cancer, it increased by 41.2%; and for rectal cancer, it increased by 36.3%.

This likely reflects the fact that, during the pandemic, “surgical capacity dropped dramatically,” Dr. Spencer said in an interview.

“To try to mitigate the consequences of that, working with their multidisciplinary teams, doctors increased the use of radiotherapy to provide a timely alternative curative treatment and help mitigate the consequences of not having access to surgery,” she said.

“This is a cohort of patients who would otherwise have had their treatment delayed, and we know that’s detrimental, so having an alternative strategy that, in specific cases, can offer similar outcomes is fantastic,” she added.

The analysis shows the “incredible speed with which radiotherapy services within the NHS were able to adapt their treatment patterns to help protect patients with cancer whilst coping with reduced surgical capacity due to the global pandemic,” coauthor Tom Roques, MD, medical director of professional practice for clinical oncology at the Royal College of Radiologists, commented in a statement.
 

Shorter radiotherapy regimen for breast cancer

In addition to the pandemic, two other events led to changes in the way that radiotherapy was delivered in the period analyzed.

One was the publication in April 2020 of the FAST-Forward trial of radiotherapy for breast cancer. This showed that radiotherapy with 26 Gy in 5 fractions administered over 1 week following primary surgery for early breast cancer was noninferior to the standard 40 Gy delivered in 15 fractions over 3 weeks.

These results led to immediate changes in practice, and quick implementation across the NHS “massively freed up capacity in terms of the number of fractions being delivered but also really helped to keep patients safe by ensuring they were only visiting the hospital on 5 occasions instead of the standard 15,” Spencer said.

Indeed, the analysis showed that the proportion of all breast radiotherapy courses given as the ultrahypofractionated regimen of 26 Gy in five fractions increased from 0.2% in April 2019 to 60.0% in April 2020 (P < .0001), which the authors noted “contributed to the substantial reduction” in radiotherapy attendances.

The other event occurred in March 2020, when NHS England “dramatically changed commissioning” from a tariff-based system in which radiotherapy was paid for every fraction delivered to a “payment that reflects the amount of money that was spent the previous year.

“That supported radiotherapy providers to do what was necessary to continue to deliver the best possible care to patients with cancer despite COVID,” Dr. Spencer added. “We saw this in our study, with doctors shortening radiotherapy courses to keep patients safe and departments running.”

The question now is whether the changes resulting from these two events will be maintained once the COVID-19 pandemic lifts.

What will happen to radiotherapy service commissioning beyond the end of the financial year is currently “unclear,” Dr. Spencer commented.

“There’s strong clinical support for continuing to use the shorter treatment courses in breast cancer, although it’s hard to know how any change in commissioning and reduction in COVID risk will influence their use over the next year and beyond,” she said.

“The data we used in this study, that Public Health England collect, will be really valuable in helping us to assess this in future,” Dr. Spencer said.
 

Radiotherapy remains reduced

Dr. Spencer taid that, “whilst in April and May 2020 we saw that the fall in radiotherapy was in cancers where it›s safe to delay treatment, in June we could see that radiotherapy activity was not back up to where it was previously, and that was across a wider range of cancers.

“This looks likely to be because of a fall in the number of people being diagnosed with cancer,” she said.

“The pandemic continues to cause severe disruption for cancer diagnosis and some national screening programs,” she commented. “This has meant that fewer patients were diagnosed with cancer during the first wave of the pandemic, and this is likely to have led to the persistent fall in treatments we are seeing.”

By November 2020, some referral pathways were back up to the volume of patients that was seen before the pandemic, but “it’s very variable across different diagnoses.”

The fear is that the resurgence of COVID-19 over the past month has made the situation worse, which is “very worrying,” Dr. Spencer said.

No funding for the study was declared. The authors disclosed no relevant financial relationships.

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

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

[email protected]

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

[email protected]

All patients receiving active cancer treatment should receive a COVID-19 vaccine and should be prioritized for vaccination, according to preliminary recommendations from the National Comprehensive Cancer Network (NCCN).

Vaccination timing considerations vary based on factors such as cancer and treatment type, and reasons for delaying vaccination in the general public also apply to cancer patients (recent COVID-19 exposure, for example).

In general, however, patients with cancer should be assigned to Centers for Disease Control and Prevention priority group 1 b/c and immunized when vaccination is available to them, the guidelines state. Exceptions to this recommendation include:

• Patients undergoing hematopoietic stem cell transplant or receiving engineered cellular therapy such as chimeric antigen receptor T-cell therapy. Vaccination should be delayed for at least 3 months in these patients to maximize vaccine efficacy. Caregivers of these patients, however, should be immunized when possible.
• Patients with hematologic malignancies who are receiving intensive cytotoxic chemotherapy, such as cytarabine- or anthracycline-based regimens for acute myeloid leukemia. Vaccination in these patients should be delayed until absolute neutrophil count recovery.
• Patients undergoing major surgery. Vaccination should occur at least a few days before or after surgery.
• Patients who have experienced a severe or immediate adverse reaction to any of the ingredients in the mRNA COVID-19 vaccines.

Conversely, vaccination should occur when available in patients with hematologic malignancies and marrow failure who are expected to have limited or no recovery, patients with hematologic malignancies who are on long-term maintenance therapy, and patients with solid tumors who are receiving cytotoxic chemotherapy, targeted therapy, checkpoint inhibitors and other immunotherapy, or radiotherapy.

Caregivers, household contacts, and other close contacts who are 16 years of age and older should be vaccinated whenever they are eligible.
 

Unique concerns in patients with cancer

The NCCN recommendations were developed to address the unique issues and concerns with respect to patients with cancer, who have an increased risk of severe illness from SARS-CoV-2 infection. But the guidelines come with a caveat: “[t]here are limited safety and efficacy data in these patients,” the NCCN emphasized in a press statement.

“Right now, there is urgent need and limited data,” Steven Pergam, MD, co-leader of the NCCN COVID-19 Vaccination Committee, said in the statement.

“Our number one goal is helping to get the vaccine to as many people as we can,” Dr. Pergam said. “That means following existing national and regional directions for prioritizing people who are more likely to face death or severe illness from COVID-19.”

Dr. Pergam, associate professor at Fred Hutchinson Cancer Research Center in Seattle, further explained that “people receiving active cancer treatment are at greater risk for worse outcomes from COVID-19, particularly if they are older and have additional comorbidities, like immunosuppression.”

NCCN’s recommendations couldn’t have come at a better time for patients with cancer, according to Nora Disis, MD, a professor at the University of Washington in Seattle.

“The NCCN’s recommendations to prioritize COVID vaccinations for cancer patients on active treatment is an important step forward in protecting our patients from the infection,” Dr. Disis said in an interview.

“Cancer patients may be at higher risk for the complications seen with infection. In addition, cancer is a disease of older people, and a good number of our patients have the comorbidities that would predict a poorer outcome if they should become sick,” Dr. Disis added. “With the correct treatment, many patients with cancer will be long-term survivors. It is important that they be protected from infection with COVID to realize their best outcome.”
 

Additional vaccine considerations

The NCCN recommendations also address several other issues of importance for cancer patients, including:

• Deprioritizing other vaccines. COVID-19 vaccines should take precedence over other vaccines because data on dual vaccination are lacking. The NCCN recommends waiting 14 days after COVID-19 vaccination to deliver other vaccines.
• Vaccinating clinical trial participants. Trial leads should be consulted to prevent protocol violations or exclusions.
• Decision-making in the setting of limited vaccine availability. The NCCN noted that decisions on allocation must be made in accordance with state and local vaccine guidance but suggests prioritizing appropriate patients on active treatment, those planning to start treatment, and those who have just completed treatment. Additional risk factors for these patients, as well as other factors associated with risk for adverse COVID-19 outcomes, should also be considered. These include advanced age, comorbidities, and adverse social and demographic factors such as poverty and limited health care access.
• The need for ongoing prevention measures. Vaccines have been shown to decrease the incidence of COVID-19 and related complications, but it remains unclear whether vaccines prevent infection and subsequent transmission. This means everyone should continue following prevention recommendations, such as wearing masks and avoiding crowds.

The NCCN stressed that these recommendations are “intended to be a living document that is constantly evolving – it will be updated rapidly whenever new data comes out, as well as any potential new vaccines that may get approved in the future.” The NCCN also noted that the advisory committee will meet regularly to refine the recommendations as needed.

Dr. Pergam disclosed relationships with Chimerix Inc., Merck & Co., Global Life Technologies Inc., and Sanofi-Aventis. Dr. Disis disclosed grants from Pfizer, Bavarian Nordisk, Janssen, and Precigen. She is the founder of EpiThany and editor-in-chief of JAMA Oncology.

[email protected]