AVAHO

Tailoring adjuvant chemotherapy based on the expression of two molecular markers did not confer a survival advantage in patients with completely resected stage II-III non–small cell lung cancer (NSCLC) in a phase 3 trial.

The patients were randomized to receive investigator’s choice of platinum-based chemotherapy or treatment tailored according to messenger RNA (mRNA) expression of two molecular markers – excision repair cross complementation 1 (ERCC1) and thymidylate synthase (TS).

There was no significant difference in overall survival or recurrence-free survival between the treatment approaches. However, toxicity was less common among patients who received customized treatment.

These results, from the phase 3 ITACA trial, were presented at the 2020 World Conference on Lung Cancer (Abstract 1820), which was rescheduled to January 2021.

“There is a clear need to define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy,” said presenter Silvia Novello, MD, PhD, of the University of Turin in Italy. “mRNA expression of different genes has been correlated with the sensitivity or resistance to specific anticancer agents.”

With this in mind, Dr. Novello and colleagues conducted the ITACA trial. The researchers’ primary goal was to determine whether an adjuvant pharmacogenomic-driven approach was able to improve overall survival in completely resected NSCLC.
 

Patients and treatment

The researchers randomized 773 NSCLC patients within 5-8 weeks after radical surgery. Genomic analyses were performed soon after surgery, and patients were randomly assigned to investigator’s choice of platinum-based chemotherapy or to tailored treatments defined by mRNA levels of ERCC1 and TS.

Patients with high ERCC1 mRNA expression who were randomized to tailored treatment received single-agent docetaxel if their TS level was high or pemetrexed monotherapy if their TS level was low.

Patients with low ERCC1 mRNA expression who were randomized to tailored treatment received cisplatin-gemcitabine if their TS level was high or cisplatin-pemetrexed if their TS was low.

The most frequent doublets used in control patients were cisplatin-gemcitabine and cisplatin-vinorelbine.

The demographic characteristics of the 384 patients randomized to tailored therapy and the 389 control subjects were well-balanced, Dr. Novello said. Two-thirds of patients had stage II disease, 11% were never smokers, and the vast majority had a lobectomy as the resection method.
 

Results

At a median follow-up of 28.2 months, the median overall survival was 96.4 months in the tailored therapy arm and 83.5 months in the control arm. The median recurrence-free survival was 64.4 months and 41.5 months, respectively.

“Adjuvant chemotherapy customization based on the primary tumor tissue mRNA expression of ERCC1 and TS did not significantly improve overall survival or recurrence-free survival,” Dr. Novello said. “There was a non–statistically significant trend for overall survival favoring the customized arm.”

Dr. Novello noted that, when the final analysis was performed, the study was underpowered, as only 46% of expected events were collected. Assuming the same hazard ratio point estimate and that the expected 336 events were collected, the hazard ratio estimate would be 0.76 (P = .012).

Grade 3/4 toxicities occurred in 32.6% of patients in the tailored therapy arm and 45.9% of those in the control arm (P < .001).

“It is important to underline that the treatment customization significantly improved the toxicity profile without compromising the efficacy,” Dr. Novello said.

She added that “more comprehensive and high-throughput diagnostic techniques will be needed in order to tailor adjuvant chemotherapy, with or without immunotherapy, in completely resected NSCLC.”

“The ITACA study is the largest adjuvant study tailored to ERCC1/TS status, and the results have been long-awaited,” said Tetsuya Mitsudomi, MD, a professor at Kindai University in Japan and president of the International Association for the Study of Lung Cancer.

“This trial should be praised for the mandated genomic analysis that was accomplished within a reasonably short time frame before random assignment. In addition, this trial confirmed that there is no biomarker strong enough to predict the efficacy of cytotoxic chemotherapy. However, the concept of customizing adjuvant therapy according to the genomic status of patients’ tumors is valid, leading to the recent demonstration in the ADAURA study of the superiority of osimertinib in delaying the postoperative recurrence of disease in patients with EGFR-mutated NSCLC.”

The ITACA study was funded by University of Turin and Eli Lilly. Dr. Novello disclosed relationships with Eli Lilly, Amgen, AstraZeneca, Bohringer Ingelheim, Beigene, Pfizer, Roche, Merck, Bristol-Myers Squibb, Takeda, and Sanofi. Dr. Mitsudomi disclosed relationships with Eli Lilly, AstraZeneca, Boehringer-Ingelheim, Chugai, Pfizer, Merck, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis, ThermoFisher, Guardant, Eisai, Amgen, and Johnson & Johnson.

Tailoring adjuvant chemotherapy based on the expression of two molecular markers did not confer a survival advantage in patients with completely resected stage II-III non–small cell lung cancer (NSCLC) in a phase 3 trial.

The patients were randomized to receive investigator’s choice of platinum-based chemotherapy or treatment tailored according to messenger RNA (mRNA) expression of two molecular markers – excision repair cross complementation 1 (ERCC1) and thymidylate synthase (TS).

There was no significant difference in overall survival or recurrence-free survival between the treatment approaches. However, toxicity was less common among patients who received customized treatment.

These results, from the phase 3 ITACA trial, were presented at the 2020 World Conference on Lung Cancer (Abstract 1820), which was rescheduled to January 2021.

“There is a clear need to define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy,” said presenter Silvia Novello, MD, PhD, of the University of Turin in Italy. “mRNA expression of different genes has been correlated with the sensitivity or resistance to specific anticancer agents.”

With this in mind, Dr. Novello and colleagues conducted the ITACA trial. The researchers’ primary goal was to determine whether an adjuvant pharmacogenomic-driven approach was able to improve overall survival in completely resected NSCLC.
 

Patients and treatment

The researchers randomized 773 NSCLC patients within 5-8 weeks after radical surgery. Genomic analyses were performed soon after surgery, and patients were randomly assigned to investigator’s choice of platinum-based chemotherapy or to tailored treatments defined by mRNA levels of ERCC1 and TS.

Patients with high ERCC1 mRNA expression who were randomized to tailored treatment received single-agent docetaxel if their TS level was high or pemetrexed monotherapy if their TS level was low.

Patients with low ERCC1 mRNA expression who were randomized to tailored treatment received cisplatin-gemcitabine if their TS level was high or cisplatin-pemetrexed if their TS was low.

The most frequent doublets used in control patients were cisplatin-gemcitabine and cisplatin-vinorelbine.

The demographic characteristics of the 384 patients randomized to tailored therapy and the 389 control subjects were well-balanced, Dr. Novello said. Two-thirds of patients had stage II disease, 11% were never smokers, and the vast majority had a lobectomy as the resection method.
 

Results

At a median follow-up of 28.2 months, the median overall survival was 96.4 months in the tailored therapy arm and 83.5 months in the control arm. The median recurrence-free survival was 64.4 months and 41.5 months, respectively.

“Adjuvant chemotherapy customization based on the primary tumor tissue mRNA expression of ERCC1 and TS did not significantly improve overall survival or recurrence-free survival,” Dr. Novello said. “There was a non–statistically significant trend for overall survival favoring the customized arm.”

Dr. Novello noted that, when the final analysis was performed, the study was underpowered, as only 46% of expected events were collected. Assuming the same hazard ratio point estimate and that the expected 336 events were collected, the hazard ratio estimate would be 0.76 (P = .012).

Grade 3/4 toxicities occurred in 32.6% of patients in the tailored therapy arm and 45.9% of those in the control arm (P < .001).

“It is important to underline that the treatment customization significantly improved the toxicity profile without compromising the efficacy,” Dr. Novello said.

She added that “more comprehensive and high-throughput diagnostic techniques will be needed in order to tailor adjuvant chemotherapy, with or without immunotherapy, in completely resected NSCLC.”

“The ITACA study is the largest adjuvant study tailored to ERCC1/TS status, and the results have been long-awaited,” said Tetsuya Mitsudomi, MD, a professor at Kindai University in Japan and president of the International Association for the Study of Lung Cancer.

“This trial should be praised for the mandated genomic analysis that was accomplished within a reasonably short time frame before random assignment. In addition, this trial confirmed that there is no biomarker strong enough to predict the efficacy of cytotoxic chemotherapy. However, the concept of customizing adjuvant therapy according to the genomic status of patients’ tumors is valid, leading to the recent demonstration in the ADAURA study of the superiority of osimertinib in delaying the postoperative recurrence of disease in patients with EGFR-mutated NSCLC.”

The ITACA study was funded by University of Turin and Eli Lilly. Dr. Novello disclosed relationships with Eli Lilly, Amgen, AstraZeneca, Bohringer Ingelheim, Beigene, Pfizer, Roche, Merck, Bristol-Myers Squibb, Takeda, and Sanofi. Dr. Mitsudomi disclosed relationships with Eli Lilly, AstraZeneca, Boehringer-Ingelheim, Chugai, Pfizer, Merck, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis, ThermoFisher, Guardant, Eisai, Amgen, and Johnson & Johnson.

Tailoring adjuvant chemotherapy based on the expression of two molecular markers did not confer a survival advantage in patients with completely resected stage II-III non–small cell lung cancer (NSCLC) in a phase 3 trial.

The patients were randomized to receive investigator’s choice of platinum-based chemotherapy or treatment tailored according to messenger RNA (mRNA) expression of two molecular markers – excision repair cross complementation 1 (ERCC1) and thymidylate synthase (TS).

There was no significant difference in overall survival or recurrence-free survival between the treatment approaches. However, toxicity was less common among patients who received customized treatment.

These results, from the phase 3 ITACA trial, were presented at the 2020 World Conference on Lung Cancer (Abstract 1820), which was rescheduled to January 2021.

“There is a clear need to define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy,” said presenter Silvia Novello, MD, PhD, of the University of Turin in Italy. “mRNA expression of different genes has been correlated with the sensitivity or resistance to specific anticancer agents.”

With this in mind, Dr. Novello and colleagues conducted the ITACA trial. The researchers’ primary goal was to determine whether an adjuvant pharmacogenomic-driven approach was able to improve overall survival in completely resected NSCLC.
 

Patients and treatment

The researchers randomized 773 NSCLC patients within 5-8 weeks after radical surgery. Genomic analyses were performed soon after surgery, and patients were randomly assigned to investigator’s choice of platinum-based chemotherapy or to tailored treatments defined by mRNA levels of ERCC1 and TS.

Patients with high ERCC1 mRNA expression who were randomized to tailored treatment received single-agent docetaxel if their TS level was high or pemetrexed monotherapy if their TS level was low.

Patients with low ERCC1 mRNA expression who were randomized to tailored treatment received cisplatin-gemcitabine if their TS level was high or cisplatin-pemetrexed if their TS was low.

The most frequent doublets used in control patients were cisplatin-gemcitabine and cisplatin-vinorelbine.

The demographic characteristics of the 384 patients randomized to tailored therapy and the 389 control subjects were well-balanced, Dr. Novello said. Two-thirds of patients had stage II disease, 11% were never smokers, and the vast majority had a lobectomy as the resection method.
 

Results

At a median follow-up of 28.2 months, the median overall survival was 96.4 months in the tailored therapy arm and 83.5 months in the control arm. The median recurrence-free survival was 64.4 months and 41.5 months, respectively.

“Adjuvant chemotherapy customization based on the primary tumor tissue mRNA expression of ERCC1 and TS did not significantly improve overall survival or recurrence-free survival,” Dr. Novello said. “There was a non–statistically significant trend for overall survival favoring the customized arm.”

Dr. Novello noted that, when the final analysis was performed, the study was underpowered, as only 46% of expected events were collected. Assuming the same hazard ratio point estimate and that the expected 336 events were collected, the hazard ratio estimate would be 0.76 (P = .012).

Grade 3/4 toxicities occurred in 32.6% of patients in the tailored therapy arm and 45.9% of those in the control arm (P < .001).

“It is important to underline that the treatment customization significantly improved the toxicity profile without compromising the efficacy,” Dr. Novello said.

She added that “more comprehensive and high-throughput diagnostic techniques will be needed in order to tailor adjuvant chemotherapy, with or without immunotherapy, in completely resected NSCLC.”

“The ITACA study is the largest adjuvant study tailored to ERCC1/TS status, and the results have been long-awaited,” said Tetsuya Mitsudomi, MD, a professor at Kindai University in Japan and president of the International Association for the Study of Lung Cancer.

“This trial should be praised for the mandated genomic analysis that was accomplished within a reasonably short time frame before random assignment. In addition, this trial confirmed that there is no biomarker strong enough to predict the efficacy of cytotoxic chemotherapy. However, the concept of customizing adjuvant therapy according to the genomic status of patients’ tumors is valid, leading to the recent demonstration in the ADAURA study of the superiority of osimertinib in delaying the postoperative recurrence of disease in patients with EGFR-mutated NSCLC.”

The ITACA study was funded by University of Turin and Eli Lilly. Dr. Novello disclosed relationships with Eli Lilly, Amgen, AstraZeneca, Bohringer Ingelheim, Beigene, Pfizer, Roche, Merck, Bristol-Myers Squibb, Takeda, and Sanofi. Dr. Mitsudomi disclosed relationships with Eli Lilly, AstraZeneca, Boehringer-Ingelheim, Chugai, Pfizer, Merck, Ono Pharmaceutical, Bristol-Myers Squibb, Novartis, ThermoFisher, Guardant, Eisai, Amgen, and Johnson & Johnson.

Concurrent cisplatin should remain the standard treatment over cetuximab for patients with locoregionally advanced head and neck squamous cell carcinoma, according to a large comparative phase 3 trial.

Based on the results of an interim analysis of the ARTSCAN III clinical trial, the independent safety data monitoring committee recommended early closure of the study because the results of the study suggest that cetuximab may be inferior to cisplatin.

“This study supports previous retrospective and prospective studies that suggest that concurrent cisplatin with radiation is superior to regimens with concurrent cetuximab in locally advanced head and neck cancers,” commented Sachin Jhawar, MD, MSCI, assistant professor in the department of radiation oncology at Ohio State University Comprehensive Cancer Center, Columbus. “While the previous studies De-ESCALaTE HPV and RTOG 1016 were specific to HPV [human papillomavirus]-positive cancers, this study allowed non–virally mediated tumors, though the majority of cases were HPV related.”

The new study also used a lower-dose weekly regimen of cisplatin than the other two studies, noted Dr. Jhawar. Early trials used a cisplatin dose of 100 mg/m² every 3 weeks, but “the field is moving toward a dose of 40 mg/m² weekly, the dose use in the Swedish study. This study had an interesting second randomization of radiation dose-escalation for more advanced primary T stage tumors, but because the study ended early it is difficult to fully interpret those results.”

Swedish researchers, led by Maria Gebre-Medhin, MD, PhD, department of hematology, oncology, and radiation physics, Skåne University Hospital, Lund, Sweden, performed an open-label, randomized, controlled, phase 3 study of patients with locoregionally advanced head and neck squamous cell carcinoma. The patients received IV cetuximab 400 mg/m² 1 week before the start of radiation therapy followed by 250 mg/m² per week, or weekly IV cisplatin 40 mg/m² during radiation therapy.

The study results were published in the Journal of Clinical Oncology.

The study was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. The cumulative incidence of locoregional failures at 3 years was more than twice as high in the cetuximab group (23%), compared with the cisplatin group (9%; P = .0036). At 3 years, overall survival was higher in the cisplatin (88%) group than in the cetuximab group (78%), but the difference was not significant (P = .086). The cumulative incidence of distant failures did not differ between the treatment groups, and the toxicity burden was similar.

“Concurrent cisplatin led to improved locoregional control and event-free survival with a trend toward improved overall survival. The types of toxicity were different, as would be expected with the different drug mechanisms, but the rate of toxicity was not,” said Dr. Dr. Jhawar. “Interestingly, the benefit of cisplatin seemed to be limited to patients with p16-positive oropharyngeal cancer. There was clinical equipoise in the p16-negative oropharyngeal cancer group and in the non–oropharyngeal cancer group. The numbers were small, but this is intriguing and suggests that there is more work to be done in this group of patients to tease out if we can escalate or use alternative therapy.”

Cisplatin has been repeatedly proven to be superior in selected populations. The next steps, said Dr. Jhawar, include defining “optimal regimens in cisplatin-ineligible populations based on age, performance status, kidney function, hearing loss, neuropathy, and HIV/AIDS; improvements with new targeted therapies and immunotherapies; and deescalation of systemic and/or radiation regimens in the best outcome groups, such as low-risk HPV-positive patients. And we are going to see more personalized medicine with genetic testing of tumors.”

When patients are ineligible for cisplatin, no optimal regimens have been defined as yet. At Ohio State, Dr. Jhawar and colleagues use carboplatin therapy.

For practicing oncologists, Dr. Jhawar said the bottom line is “patients who are eligible should receive concurrent cisplatin therapy for locoregionally advanced head and neck cancer.”

The ARTSCAN III study was funded by the Swedish Cancer Society and the Mrs. Berta Kamprad Cancer Foundation. One of the study’s coauthors reported a leadership role in ScandiDos. The other authors reported they had no conflicts. Dr. Jhawar reported he had no conflicts of interest.




 

Concurrent cisplatin should remain the standard treatment over cetuximab for patients with locoregionally advanced head and neck squamous cell carcinoma, according to a large comparative phase 3 trial.

Based on the results of an interim analysis of the ARTSCAN III clinical trial, the independent safety data monitoring committee recommended early closure of the study because the results of the study suggest that cetuximab may be inferior to cisplatin.

“This study supports previous retrospective and prospective studies that suggest that concurrent cisplatin with radiation is superior to regimens with concurrent cetuximab in locally advanced head and neck cancers,” commented Sachin Jhawar, MD, MSCI, assistant professor in the department of radiation oncology at Ohio State University Comprehensive Cancer Center, Columbus. “While the previous studies De-ESCALaTE HPV and RTOG 1016 were specific to HPV [human papillomavirus]-positive cancers, this study allowed non–virally mediated tumors, though the majority of cases were HPV related.”

The new study also used a lower-dose weekly regimen of cisplatin than the other two studies, noted Dr. Jhawar. Early trials used a cisplatin dose of 100 mg/m² every 3 weeks, but “the field is moving toward a dose of 40 mg/m² weekly, the dose use in the Swedish study. This study had an interesting second randomization of radiation dose-escalation for more advanced primary T stage tumors, but because the study ended early it is difficult to fully interpret those results.”

Swedish researchers, led by Maria Gebre-Medhin, MD, PhD, department of hematology, oncology, and radiation physics, Skåne University Hospital, Lund, Sweden, performed an open-label, randomized, controlled, phase 3 study of patients with locoregionally advanced head and neck squamous cell carcinoma. The patients received IV cetuximab 400 mg/m² 1 week before the start of radiation therapy followed by 250 mg/m² per week, or weekly IV cisplatin 40 mg/m² during radiation therapy.

The study results were published in the Journal of Clinical Oncology.

The study was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. The cumulative incidence of locoregional failures at 3 years was more than twice as high in the cetuximab group (23%), compared with the cisplatin group (9%; P = .0036). At 3 years, overall survival was higher in the cisplatin (88%) group than in the cetuximab group (78%), but the difference was not significant (P = .086). The cumulative incidence of distant failures did not differ between the treatment groups, and the toxicity burden was similar.

“Concurrent cisplatin led to improved locoregional control and event-free survival with a trend toward improved overall survival. The types of toxicity were different, as would be expected with the different drug mechanisms, but the rate of toxicity was not,” said Dr. Dr. Jhawar. “Interestingly, the benefit of cisplatin seemed to be limited to patients with p16-positive oropharyngeal cancer. There was clinical equipoise in the p16-negative oropharyngeal cancer group and in the non–oropharyngeal cancer group. The numbers were small, but this is intriguing and suggests that there is more work to be done in this group of patients to tease out if we can escalate or use alternative therapy.”

Cisplatin has been repeatedly proven to be superior in selected populations. The next steps, said Dr. Jhawar, include defining “optimal regimens in cisplatin-ineligible populations based on age, performance status, kidney function, hearing loss, neuropathy, and HIV/AIDS; improvements with new targeted therapies and immunotherapies; and deescalation of systemic and/or radiation regimens in the best outcome groups, such as low-risk HPV-positive patients. And we are going to see more personalized medicine with genetic testing of tumors.”

When patients are ineligible for cisplatin, no optimal regimens have been defined as yet. At Ohio State, Dr. Jhawar and colleagues use carboplatin therapy.

For practicing oncologists, Dr. Jhawar said the bottom line is “patients who are eligible should receive concurrent cisplatin therapy for locoregionally advanced head and neck cancer.”

The ARTSCAN III study was funded by the Swedish Cancer Society and the Mrs. Berta Kamprad Cancer Foundation. One of the study’s coauthors reported a leadership role in ScandiDos. The other authors reported they had no conflicts. Dr. Jhawar reported he had no conflicts of interest.




 

Concurrent cisplatin should remain the standard treatment over cetuximab for patients with locoregionally advanced head and neck squamous cell carcinoma, according to a large comparative phase 3 trial.

Based on the results of an interim analysis of the ARTSCAN III clinical trial, the independent safety data monitoring committee recommended early closure of the study because the results of the study suggest that cetuximab may be inferior to cisplatin.

“This study supports previous retrospective and prospective studies that suggest that concurrent cisplatin with radiation is superior to regimens with concurrent cetuximab in locally advanced head and neck cancers,” commented Sachin Jhawar, MD, MSCI, assistant professor in the department of radiation oncology at Ohio State University Comprehensive Cancer Center, Columbus. “While the previous studies De-ESCALaTE HPV and RTOG 1016 were specific to HPV [human papillomavirus]-positive cancers, this study allowed non–virally mediated tumors, though the majority of cases were HPV related.”

The new study also used a lower-dose weekly regimen of cisplatin than the other two studies, noted Dr. Jhawar. Early trials used a cisplatin dose of 100 mg/m² every 3 weeks, but “the field is moving toward a dose of 40 mg/m² weekly, the dose use in the Swedish study. This study had an interesting second randomization of radiation dose-escalation for more advanced primary T stage tumors, but because the study ended early it is difficult to fully interpret those results.”

Swedish researchers, led by Maria Gebre-Medhin, MD, PhD, department of hematology, oncology, and radiation physics, Skåne University Hospital, Lund, Sweden, performed an open-label, randomized, controlled, phase 3 study of patients with locoregionally advanced head and neck squamous cell carcinoma. The patients received IV cetuximab 400 mg/m² 1 week before the start of radiation therapy followed by 250 mg/m² per week, or weekly IV cisplatin 40 mg/m² during radiation therapy.

The study results were published in the Journal of Clinical Oncology.

The study was prematurely closed after an unplanned interim analysis when 298 patients had been randomly assigned. The cumulative incidence of locoregional failures at 3 years was more than twice as high in the cetuximab group (23%), compared with the cisplatin group (9%; P = .0036). At 3 years, overall survival was higher in the cisplatin (88%) group than in the cetuximab group (78%), but the difference was not significant (P = .086). The cumulative incidence of distant failures did not differ between the treatment groups, and the toxicity burden was similar.

“Concurrent cisplatin led to improved locoregional control and event-free survival with a trend toward improved overall survival. The types of toxicity were different, as would be expected with the different drug mechanisms, but the rate of toxicity was not,” said Dr. Dr. Jhawar. “Interestingly, the benefit of cisplatin seemed to be limited to patients with p16-positive oropharyngeal cancer. There was clinical equipoise in the p16-negative oropharyngeal cancer group and in the non–oropharyngeal cancer group. The numbers were small, but this is intriguing and suggests that there is more work to be done in this group of patients to tease out if we can escalate or use alternative therapy.”

Cisplatin has been repeatedly proven to be superior in selected populations. The next steps, said Dr. Jhawar, include defining “optimal regimens in cisplatin-ineligible populations based on age, performance status, kidney function, hearing loss, neuropathy, and HIV/AIDS; improvements with new targeted therapies and immunotherapies; and deescalation of systemic and/or radiation regimens in the best outcome groups, such as low-risk HPV-positive patients. And we are going to see more personalized medicine with genetic testing of tumors.”

When patients are ineligible for cisplatin, no optimal regimens have been defined as yet. At Ohio State, Dr. Jhawar and colleagues use carboplatin therapy.

For practicing oncologists, Dr. Jhawar said the bottom line is “patients who are eligible should receive concurrent cisplatin therapy for locoregionally advanced head and neck cancer.”

The ARTSCAN III study was funded by the Swedish Cancer Society and the Mrs. Berta Kamprad Cancer Foundation. One of the study’s coauthors reported a leadership role in ScandiDos. The other authors reported they had no conflicts. Dr. Jhawar reported he had no conflicts of interest.




 

Neoadjuvant atezolizumab prior to lung cancer surgery was well tolerated by patients with stage IB-IIIB lung cancer and produced a 21% major pathologic response rate, according to the primary analysis of the Lung Cancer Mutation Consortium (LCMC) 3 study.

Small pilot studies previously suggested that preoperative immune checkpoint inhibitor (ICI) therapy may benefit patients with resectable non–small cell lung cancer (NSCLC).

The LCMC3 study is “unique” because it is the largest monotherapy trial of checkpoint inhibition in resectable NSCLC, and it’s “a landmark study” because it validated results from smaller trials and can serve as a benchmark for future ones, said Jay M. Lee, MD, of the University of California, Los Angeles.

Dr. Lee presented results from LCMC3 at the 2020 World Congress on Lung Cancer (Abstract PS01.05), which was rescheduled for January 2021.

The study included 181 patients, median age 65 years, with stage IB-IIIB NSCLC. The vast majority (90%) of patients were current/former smokers, and two-thirds had a nonsquamous histology. Patients were categorized in the following stages: 17 patients were staged at IB, 20 were IIA, 55 were IIB, 72 were IIIA, and 17 were IIIB.

Patients received 1,200 mg of neoadjuvant atezolizumab intravenously every 3 weeks for two cycles followed by resection between 30 and 50 days from the first cycle. Patients who benefited from the therapy continued adjuvant atezolizumab for 12 months.

The primary endpoint was major pathological response, defined as no more than 10% viable tumor cells at surgery, in patients without epidermal growth factor receptor or anaplastic lymphoma kinase mutations.
 

Results

Following atezolizumab treatment, 43% of patients were down-staged, and 19% were up-staged. Some degree of pathological regression was observed in all but 3 of the 159 patients who underwent resection.

Among the 144 patients included in the efficacy analysis, the major pathological response rate was 21%, with 7% of patients achieving a complete pathological response.

“We demonstrated that more than half of patients resected with a minimally invasive operation. Remarkably, only 15% required thoracotomy. The 92% complete resection rate is comparable, if not superior to, preoperative chemotherapy trials,” Dr. Lee said.

The majority (88%) of patients underwent surgical resection within a 20-day protocol window. The median time from end of neoadjuvant therapy to surgery was 22 days.

“Historically, the neoadjuvant chemotherapy window is much later for surgery, 3 weeks from neoadjuvant therapy, and that can be stretched to up to 56 days,” Dr. Lee said.

In an exploratory analysis, the 1.5-year overall survival rate was 91% for stage I and II disease and 87% for stage III disease. The survival in both cohorts was superior to that expected historically, Dr. Lee noted.

Intraoperative complications were rare (3%). Postoperative adverse reactions correlated with fewer viable tumor cells in the resected specimen.

One patient died following surgery after the first 30 days, which was deemed unrelated to treatment. Another patient died between 30 and 90 days from treatment-related pneumonitis.

“The LCMC3 study successfully met its primary endpoint of achieving major pathological response,” Dr. Lee concluded. “Neoadjuvant atezolizumab monotherapy was well tolerated, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window and with a short time frame from completion of atezolizumab and with a correspondingly high complete resection rate.”

The study’s results suggest that “neoadjuvant atezolizumab monotherapy is effective, well tolerated, and surgically acceptable,” said study discussant Shinichi Toyooka, MD, of Okayama (Japan) University Hospital.

“I would consider single-agent ICI neoadjuvant therapy for patients with early-stage disease and poor performance status, and an ICI plus chemotherapy for more advanced resectable cases, like locally advanced disease,” Dr. Toyooka said.

The LCMC3 study is sponsored by Genentech. Dr. Lee disclosed relationships with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis. Dr. Toyooka disclosed relationships with AstraZeneca, Chugai, Taiho Pharmaceutical Group, and Ono Pharmaceutical.

Neoadjuvant atezolizumab prior to lung cancer surgery was well tolerated by patients with stage IB-IIIB lung cancer and produced a 21% major pathologic response rate, according to the primary analysis of the Lung Cancer Mutation Consortium (LCMC) 3 study.

Small pilot studies previously suggested that preoperative immune checkpoint inhibitor (ICI) therapy may benefit patients with resectable non–small cell lung cancer (NSCLC).

The LCMC3 study is “unique” because it is the largest monotherapy trial of checkpoint inhibition in resectable NSCLC, and it’s “a landmark study” because it validated results from smaller trials and can serve as a benchmark for future ones, said Jay M. Lee, MD, of the University of California, Los Angeles.

Dr. Lee presented results from LCMC3 at the 2020 World Congress on Lung Cancer (Abstract PS01.05), which was rescheduled for January 2021.

The study included 181 patients, median age 65 years, with stage IB-IIIB NSCLC. The vast majority (90%) of patients were current/former smokers, and two-thirds had a nonsquamous histology. Patients were categorized in the following stages: 17 patients were staged at IB, 20 were IIA, 55 were IIB, 72 were IIIA, and 17 were IIIB.

Patients received 1,200 mg of neoadjuvant atezolizumab intravenously every 3 weeks for two cycles followed by resection between 30 and 50 days from the first cycle. Patients who benefited from the therapy continued adjuvant atezolizumab for 12 months.

The primary endpoint was major pathological response, defined as no more than 10% viable tumor cells at surgery, in patients without epidermal growth factor receptor or anaplastic lymphoma kinase mutations.
 

Results

Following atezolizumab treatment, 43% of patients were down-staged, and 19% were up-staged. Some degree of pathological regression was observed in all but 3 of the 159 patients who underwent resection.

Among the 144 patients included in the efficacy analysis, the major pathological response rate was 21%, with 7% of patients achieving a complete pathological response.

“We demonstrated that more than half of patients resected with a minimally invasive operation. Remarkably, only 15% required thoracotomy. The 92% complete resection rate is comparable, if not superior to, preoperative chemotherapy trials,” Dr. Lee said.

The majority (88%) of patients underwent surgical resection within a 20-day protocol window. The median time from end of neoadjuvant therapy to surgery was 22 days.

“Historically, the neoadjuvant chemotherapy window is much later for surgery, 3 weeks from neoadjuvant therapy, and that can be stretched to up to 56 days,” Dr. Lee said.

In an exploratory analysis, the 1.5-year overall survival rate was 91% for stage I and II disease and 87% for stage III disease. The survival in both cohorts was superior to that expected historically, Dr. Lee noted.

Intraoperative complications were rare (3%). Postoperative adverse reactions correlated with fewer viable tumor cells in the resected specimen.

One patient died following surgery after the first 30 days, which was deemed unrelated to treatment. Another patient died between 30 and 90 days from treatment-related pneumonitis.

“The LCMC3 study successfully met its primary endpoint of achieving major pathological response,” Dr. Lee concluded. “Neoadjuvant atezolizumab monotherapy was well tolerated, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window and with a short time frame from completion of atezolizumab and with a correspondingly high complete resection rate.”

The study’s results suggest that “neoadjuvant atezolizumab monotherapy is effective, well tolerated, and surgically acceptable,” said study discussant Shinichi Toyooka, MD, of Okayama (Japan) University Hospital.

“I would consider single-agent ICI neoadjuvant therapy for patients with early-stage disease and poor performance status, and an ICI plus chemotherapy for more advanced resectable cases, like locally advanced disease,” Dr. Toyooka said.

The LCMC3 study is sponsored by Genentech. Dr. Lee disclosed relationships with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis. Dr. Toyooka disclosed relationships with AstraZeneca, Chugai, Taiho Pharmaceutical Group, and Ono Pharmaceutical.

Neoadjuvant atezolizumab prior to lung cancer surgery was well tolerated by patients with stage IB-IIIB lung cancer and produced a 21% major pathologic response rate, according to the primary analysis of the Lung Cancer Mutation Consortium (LCMC) 3 study.

Small pilot studies previously suggested that preoperative immune checkpoint inhibitor (ICI) therapy may benefit patients with resectable non–small cell lung cancer (NSCLC).

The LCMC3 study is “unique” because it is the largest monotherapy trial of checkpoint inhibition in resectable NSCLC, and it’s “a landmark study” because it validated results from smaller trials and can serve as a benchmark for future ones, said Jay M. Lee, MD, of the University of California, Los Angeles.

Dr. Lee presented results from LCMC3 at the 2020 World Congress on Lung Cancer (Abstract PS01.05), which was rescheduled for January 2021.

The study included 181 patients, median age 65 years, with stage IB-IIIB NSCLC. The vast majority (90%) of patients were current/former smokers, and two-thirds had a nonsquamous histology. Patients were categorized in the following stages: 17 patients were staged at IB, 20 were IIA, 55 were IIB, 72 were IIIA, and 17 were IIIB.

Patients received 1,200 mg of neoadjuvant atezolizumab intravenously every 3 weeks for two cycles followed by resection between 30 and 50 days from the first cycle. Patients who benefited from the therapy continued adjuvant atezolizumab for 12 months.

The primary endpoint was major pathological response, defined as no more than 10% viable tumor cells at surgery, in patients without epidermal growth factor receptor or anaplastic lymphoma kinase mutations.
 

Results

Following atezolizumab treatment, 43% of patients were down-staged, and 19% were up-staged. Some degree of pathological regression was observed in all but 3 of the 159 patients who underwent resection.

Among the 144 patients included in the efficacy analysis, the major pathological response rate was 21%, with 7% of patients achieving a complete pathological response.

“We demonstrated that more than half of patients resected with a minimally invasive operation. Remarkably, only 15% required thoracotomy. The 92% complete resection rate is comparable, if not superior to, preoperative chemotherapy trials,” Dr. Lee said.

The majority (88%) of patients underwent surgical resection within a 20-day protocol window. The median time from end of neoadjuvant therapy to surgery was 22 days.

“Historically, the neoadjuvant chemotherapy window is much later for surgery, 3 weeks from neoadjuvant therapy, and that can be stretched to up to 56 days,” Dr. Lee said.

In an exploratory analysis, the 1.5-year overall survival rate was 91% for stage I and II disease and 87% for stage III disease. The survival in both cohorts was superior to that expected historically, Dr. Lee noted.

Intraoperative complications were rare (3%). Postoperative adverse reactions correlated with fewer viable tumor cells in the resected specimen.

One patient died following surgery after the first 30 days, which was deemed unrelated to treatment. Another patient died between 30 and 90 days from treatment-related pneumonitis.

“The LCMC3 study successfully met its primary endpoint of achieving major pathological response,” Dr. Lee concluded. “Neoadjuvant atezolizumab monotherapy was well tolerated, and resection was performed with low perioperative morbidity and mortality, usually within a narrow protocol window and with a short time frame from completion of atezolizumab and with a correspondingly high complete resection rate.”

The study’s results suggest that “neoadjuvant atezolizumab monotherapy is effective, well tolerated, and surgically acceptable,” said study discussant Shinichi Toyooka, MD, of Okayama (Japan) University Hospital.

“I would consider single-agent ICI neoadjuvant therapy for patients with early-stage disease and poor performance status, and an ICI plus chemotherapy for more advanced resectable cases, like locally advanced disease,” Dr. Toyooka said.

The LCMC3 study is sponsored by Genentech. Dr. Lee disclosed relationships with Genentech/Roche, AstraZeneca, Bristol-Myers Squibb, Merck, and Novartis. Dr. Toyooka disclosed relationships with AstraZeneca, Chugai, Taiho Pharmaceutical Group, and Ono Pharmaceutical.

Best practices for managing cancer outpatients continue to evolve during the COVID-19 pandemic, with recent innovations in technology, operations, and communication.

“We’ve tried a lot of new things to ensure optimal care for our patients,” said Tiffany A. Traina, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York. “We need to effectively utilize all resources at our disposal to keep in touch with our patients during this time.”

Dr. Traina described the approach to outpatient management used at MSKCC during a presentation at the AACR Virtual Meeting: COVID-19 and Cancer.
 

Four guiding principles

MSKCC has established four guiding principles on how to manage cancer patients during the pandemic: openness, safety, technology, and staffing.

Openness ensures that decisions are guided by clinical priorities to provide optimal patient care and allow for prioritization of clinical research and education, Dr. Traina said.

The safety of patients and staff is of the utmost importance, she added. To ensure safety in the context of outpatient care, several operational levers were developed, including COVID surge planning, universal masking and personal protective equipment guidelines, remote work, clinical levers, and new dashboards and communications.

Dr. Traina said data analytics and dashboards have been key technological tools used to support evidence-based decision-making and deliver care remotely for patients during the pandemic.

Staffing resources have also shifted to support demand at different health system locations.
 

Screening, cohorting, and telemedicine

One measure MSKCC adopted is the MSK Engage Questionnaire, a COVID-19 screening questionnaire assigned to every patient with a scheduled outpatient visit. After completing the questionnaire, patients receive a response denoting whether they need to come into the outpatient setting.

On the staffing side, clinic coordinators prepare appointments accordingly, based on the risk level for each patient.

“We also try to cohort COVID-positive patients into particular areas within the outpatient setting,” Dr. Traina explained. “In addition, we control flow through ambulatory care locations by having separate patient entrances and use other tools to make flow as efficient as possible.”

On the technology side, interactive dashboards are being used to model traffic through different buildings.

“These data and analytics are useful for operational engineering, answering questions such as (1) Are there backups in chemotherapy? and (2) Are patients seeing one particular physician?” Dr. Traina explained. “One important key takeaway is the importance of frequently communicating simple messages through multiple mechanisms, including signage, websites, and dedicated resources.”

Other key technological measures are leveraging telemedicine to convert inpatient appointments to a virtual setting, as well as developing and deploying a system for centralized outpatient follow-up of COVID-19-positive patients.

“We saw a 3,000% increase in telemedicine utilization from February 2020 to June 2020,” Dr. Traina reported. “In a given month, we have approximately 230,000 outpatient visits, and a substantial proportion of these are now done via telemedicine.”

Dr. Traina also noted that multiple organizations have released guidelines addressing when to resume anticancer therapy in patients who have been COVID-19 positive. Adherence is important, as unnecessary COVID-19 testing may delay cancer therapy and is not recommended.

During a live discussion, Louis P. Voigt, MD, of MSKCC, said Dr. Traina’s presentation provided “a lot of good ideas for other institutions who may be facing similar challenges.”

Dr. Traina and Dr. Voigt disclosed no conflicts of interest. No funding sources were reported.

Best practices for managing cancer outpatients continue to evolve during the COVID-19 pandemic, with recent innovations in technology, operations, and communication.

“We’ve tried a lot of new things to ensure optimal care for our patients,” said Tiffany A. Traina, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York. “We need to effectively utilize all resources at our disposal to keep in touch with our patients during this time.”

Dr. Traina described the approach to outpatient management used at MSKCC during a presentation at the AACR Virtual Meeting: COVID-19 and Cancer.
 

Four guiding principles

MSKCC has established four guiding principles on how to manage cancer patients during the pandemic: openness, safety, technology, and staffing.

Openness ensures that decisions are guided by clinical priorities to provide optimal patient care and allow for prioritization of clinical research and education, Dr. Traina said.

The safety of patients and staff is of the utmost importance, she added. To ensure safety in the context of outpatient care, several operational levers were developed, including COVID surge planning, universal masking and personal protective equipment guidelines, remote work, clinical levers, and new dashboards and communications.

Dr. Traina said data analytics and dashboards have been key technological tools used to support evidence-based decision-making and deliver care remotely for patients during the pandemic.

Staffing resources have also shifted to support demand at different health system locations.
 

Screening, cohorting, and telemedicine

One measure MSKCC adopted is the MSK Engage Questionnaire, a COVID-19 screening questionnaire assigned to every patient with a scheduled outpatient visit. After completing the questionnaire, patients receive a response denoting whether they need to come into the outpatient setting.

On the staffing side, clinic coordinators prepare appointments accordingly, based on the risk level for each patient.

“We also try to cohort COVID-positive patients into particular areas within the outpatient setting,” Dr. Traina explained. “In addition, we control flow through ambulatory care locations by having separate patient entrances and use other tools to make flow as efficient as possible.”

On the technology side, interactive dashboards are being used to model traffic through different buildings.

“These data and analytics are useful for operational engineering, answering questions such as (1) Are there backups in chemotherapy? and (2) Are patients seeing one particular physician?” Dr. Traina explained. “One important key takeaway is the importance of frequently communicating simple messages through multiple mechanisms, including signage, websites, and dedicated resources.”

Other key technological measures are leveraging telemedicine to convert inpatient appointments to a virtual setting, as well as developing and deploying a system for centralized outpatient follow-up of COVID-19-positive patients.

“We saw a 3,000% increase in telemedicine utilization from February 2020 to June 2020,” Dr. Traina reported. “In a given month, we have approximately 230,000 outpatient visits, and a substantial proportion of these are now done via telemedicine.”

Dr. Traina also noted that multiple organizations have released guidelines addressing when to resume anticancer therapy in patients who have been COVID-19 positive. Adherence is important, as unnecessary COVID-19 testing may delay cancer therapy and is not recommended.

During a live discussion, Louis P. Voigt, MD, of MSKCC, said Dr. Traina’s presentation provided “a lot of good ideas for other institutions who may be facing similar challenges.”

Dr. Traina and Dr. Voigt disclosed no conflicts of interest. No funding sources were reported.

Best practices for managing cancer outpatients continue to evolve during the COVID-19 pandemic, with recent innovations in technology, operations, and communication.

“We’ve tried a lot of new things to ensure optimal care for our patients,” said Tiffany A. Traina, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York. “We need to effectively utilize all resources at our disposal to keep in touch with our patients during this time.”

Dr. Traina described the approach to outpatient management used at MSKCC during a presentation at the AACR Virtual Meeting: COVID-19 and Cancer.
 

Four guiding principles

MSKCC has established four guiding principles on how to manage cancer patients during the pandemic: openness, safety, technology, and staffing.

Openness ensures that decisions are guided by clinical priorities to provide optimal patient care and allow for prioritization of clinical research and education, Dr. Traina said.

The safety of patients and staff is of the utmost importance, she added. To ensure safety in the context of outpatient care, several operational levers were developed, including COVID surge planning, universal masking and personal protective equipment guidelines, remote work, clinical levers, and new dashboards and communications.

Dr. Traina said data analytics and dashboards have been key technological tools used to support evidence-based decision-making and deliver care remotely for patients during the pandemic.

Staffing resources have also shifted to support demand at different health system locations.
 

Screening, cohorting, and telemedicine

One measure MSKCC adopted is the MSK Engage Questionnaire, a COVID-19 screening questionnaire assigned to every patient with a scheduled outpatient visit. After completing the questionnaire, patients receive a response denoting whether they need to come into the outpatient setting.

On the staffing side, clinic coordinators prepare appointments accordingly, based on the risk level for each patient.

“We also try to cohort COVID-positive patients into particular areas within the outpatient setting,” Dr. Traina explained. “In addition, we control flow through ambulatory care locations by having separate patient entrances and use other tools to make flow as efficient as possible.”

On the technology side, interactive dashboards are being used to model traffic through different buildings.

“These data and analytics are useful for operational engineering, answering questions such as (1) Are there backups in chemotherapy? and (2) Are patients seeing one particular physician?” Dr. Traina explained. “One important key takeaway is the importance of frequently communicating simple messages through multiple mechanisms, including signage, websites, and dedicated resources.”

Other key technological measures are leveraging telemedicine to convert inpatient appointments to a virtual setting, as well as developing and deploying a system for centralized outpatient follow-up of COVID-19-positive patients.

“We saw a 3,000% increase in telemedicine utilization from February 2020 to June 2020,” Dr. Traina reported. “In a given month, we have approximately 230,000 outpatient visits, and a substantial proportion of these are now done via telemedicine.”

Dr. Traina also noted that multiple organizations have released guidelines addressing when to resume anticancer therapy in patients who have been COVID-19 positive. Adherence is important, as unnecessary COVID-19 testing may delay cancer therapy and is not recommended.

During a live discussion, Louis P. Voigt, MD, of MSKCC, said Dr. Traina’s presentation provided “a lot of good ideas for other institutions who may be facing similar challenges.”

Dr. Traina and Dr. Voigt disclosed no conflicts of interest. No funding sources were reported.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A tangled web ... with no clear conclusions yet

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

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

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

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

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

Study followed women whose sisters had breast cancer 

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

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

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

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

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

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

Association of metformin and breast cancer

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

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

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

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

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

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

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

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

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

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

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

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

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

A tangled web ... with no clear conclusions yet

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

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

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

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

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

Study followed women whose sisters had breast cancer 

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

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

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

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

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

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

Association of metformin and breast cancer

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

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

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

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

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

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

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

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

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

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

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

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

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

A tangled web ... with no clear conclusions yet

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

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

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

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

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

Study followed women whose sisters had breast cancer 

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

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

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

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

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

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

Association of metformin and breast cancer

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Until nuances revealed, no change in practice

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

Updated on 2/8/2021.

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

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

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

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

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

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

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

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

Until nuances revealed, no change in practice

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

Updated on 2/8/2021.

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

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

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

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

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

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

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

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

Until nuances revealed, no change in practice

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

Updated on 2/8/2021.

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

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

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

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

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

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

About the study

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

About the study

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

About the study

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

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

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

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

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

Results

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

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

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

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

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

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

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

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

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

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

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

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

Copyright University of Florida

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

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

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

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

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

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

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

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

Results: Top models and features

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

Copyright University of Florida

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

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

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

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

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

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

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

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

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

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

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

Copyright University of Florida

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

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

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

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

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

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

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

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

Results: Top models and features

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

Copyright University of Florida

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

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

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

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

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

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

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

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

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

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

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

Copyright University of Florida

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

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

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

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

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

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

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

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

Results: Top models and features

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

Copyright University of Florida

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Updated results

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Updated results

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Updated results

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

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

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

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

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

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

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

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

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

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

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

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