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Adding bevacizumab improves PFS in extensive SCLC
Adding the antiangiogenic agent bevacizumab to standard first-line chemotherapy improves progression-free survival in extensive small-cell lung cancer, according to a report published online Jan. 30.
In what they described as the first prospective randomized, controlled phase III trial comparing these two approaches, researchers studied 204 adults who had extensive SCLC, including brain and bone metastases, at 29 medical centers in Italy. These participants (mean age, 64 years) were randomly assigned to receive a combination of standard cisplatin, etoposide, and bevacizumab every 3 weeks or cisplatin and etoposide chemotherapy every 3 weeks. Patients who developed cisplatin contraindications or toxicity related to the drug could substitute carboplatin. In the experimental arm of the study, patients could opt to continue bevacizumab alone as maintenance therapy for a maximum of 18 cycles. Forty-one patients (42%) did so, said Marcello Tiseo, MD, PhD, of Azienda Ospedaliero Universitaria, Parma, Italy, and his associates.
After a median follow-up of 35 months, the median progression-free survival was 5.7 months with standard therapy and 6.7 months with add-on bevacizumab (hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.97; P = .030). However, adding bevacizumab did not significantly improve overall survival, which was the primary endpoint of the trial. A subgroup analysis showed that bevacizumab significantly extended overall survival among men (HR, 0.55) but not among women (HR, 1.55), an association that has been reported in previous studies, Dr. Tiseo and his associates said (J Clin Oncol. 2017 Jan 30. doi:10.1200/JCO.2016.69.4844).
These findings, together with those of other investigators assessing the same class of agents, justify “further studies with novel and better antiangiogenic agents in extensive SCLC, particularly in the maintenance setting,” they added.
This trial was supported by the Agenzia Italiana del Farmaco. Dr. Tiseo reported serving as a consultant for AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Pierre Fabre, and Otsuka; his associates reported ties to numerous industry sources.
Adding the antiangiogenic agent bevacizumab to standard first-line chemotherapy improves progression-free survival in extensive small-cell lung cancer, according to a report published online Jan. 30.
In what they described as the first prospective randomized, controlled phase III trial comparing these two approaches, researchers studied 204 adults who had extensive SCLC, including brain and bone metastases, at 29 medical centers in Italy. These participants (mean age, 64 years) were randomly assigned to receive a combination of standard cisplatin, etoposide, and bevacizumab every 3 weeks or cisplatin and etoposide chemotherapy every 3 weeks. Patients who developed cisplatin contraindications or toxicity related to the drug could substitute carboplatin. In the experimental arm of the study, patients could opt to continue bevacizumab alone as maintenance therapy for a maximum of 18 cycles. Forty-one patients (42%) did so, said Marcello Tiseo, MD, PhD, of Azienda Ospedaliero Universitaria, Parma, Italy, and his associates.
After a median follow-up of 35 months, the median progression-free survival was 5.7 months with standard therapy and 6.7 months with add-on bevacizumab (hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.97; P = .030). However, adding bevacizumab did not significantly improve overall survival, which was the primary endpoint of the trial. A subgroup analysis showed that bevacizumab significantly extended overall survival among men (HR, 0.55) but not among women (HR, 1.55), an association that has been reported in previous studies, Dr. Tiseo and his associates said (J Clin Oncol. 2017 Jan 30. doi:10.1200/JCO.2016.69.4844).
These findings, together with those of other investigators assessing the same class of agents, justify “further studies with novel and better antiangiogenic agents in extensive SCLC, particularly in the maintenance setting,” they added.
This trial was supported by the Agenzia Italiana del Farmaco. Dr. Tiseo reported serving as a consultant for AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Pierre Fabre, and Otsuka; his associates reported ties to numerous industry sources.
Adding the antiangiogenic agent bevacizumab to standard first-line chemotherapy improves progression-free survival in extensive small-cell lung cancer, according to a report published online Jan. 30.
In what they described as the first prospective randomized, controlled phase III trial comparing these two approaches, researchers studied 204 adults who had extensive SCLC, including brain and bone metastases, at 29 medical centers in Italy. These participants (mean age, 64 years) were randomly assigned to receive a combination of standard cisplatin, etoposide, and bevacizumab every 3 weeks or cisplatin and etoposide chemotherapy every 3 weeks. Patients who developed cisplatin contraindications or toxicity related to the drug could substitute carboplatin. In the experimental arm of the study, patients could opt to continue bevacizumab alone as maintenance therapy for a maximum of 18 cycles. Forty-one patients (42%) did so, said Marcello Tiseo, MD, PhD, of Azienda Ospedaliero Universitaria, Parma, Italy, and his associates.
After a median follow-up of 35 months, the median progression-free survival was 5.7 months with standard therapy and 6.7 months with add-on bevacizumab (hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.97; P = .030). However, adding bevacizumab did not significantly improve overall survival, which was the primary endpoint of the trial. A subgroup analysis showed that bevacizumab significantly extended overall survival among men (HR, 0.55) but not among women (HR, 1.55), an association that has been reported in previous studies, Dr. Tiseo and his associates said (J Clin Oncol. 2017 Jan 30. doi:10.1200/JCO.2016.69.4844).
These findings, together with those of other investigators assessing the same class of agents, justify “further studies with novel and better antiangiogenic agents in extensive SCLC, particularly in the maintenance setting,” they added.
This trial was supported by the Agenzia Italiana del Farmaco. Dr. Tiseo reported serving as a consultant for AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Pierre Fabre, and Otsuka; his associates reported ties to numerous industry sources.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Adding bevacizumab to standard first-line chemotherapy improves progression-free survival in extensive small-cell lung cancer.
Major finding: After a median follow-up of 35 months, the median progression-free survival was 5.7 months with standard therapy and 6.7 months with add-on bevacizumab (hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.97; P = .030).
Data source: A multicenter open-label randomized, controlled phase III trial involving 204 adults in Italy.
Disclosures: This trial was supported by the Agenzia Italiana del Farmaco. Dr. Tiseo reported serving as a consultant for AstraZeneca, Eli Lilly, Boehringer Ingelheim, Novartis, Bristol-Myers Squibb, Pierre Fabre, and Otsuka; his associates reported ties to numerous industry sources.
Lung cancer screening a challenge to implement
A comprehensive lung cancer screening program carried out at Veterans Health Administration hospitals was taxing to implement and revealed a large number of patients with results requiring follow-up, though only 1.5% had cancers.
Investigators at eight VHA hospitals, led by Linda S. Kinsinger, MD, of the VHA’s National Center for Health Promotion and Disease Prevention in Durham, N.C., looked at records from about 93,000 primary care patients and identified 4,246 eligible for screening, based on age, medical history, and smoking history (JAMA Intern Med. 2017 Jan 30. doi: 10.1001/jamainternmed.2016.9022).
Approximately 58% of the eligible patients consented, and 2,106 underwent screening with low-dose computed tomography (LDCT). The mean age of patients was 65 years, and 96% of patients were male.
Nearly 60% of patients screened (1,257) had nodules, 1,184 patients (56.2%) required tracking, and 31 patients (1.5%) had lung cancer.
The pilot study was developed in response to a 2013 recommendation from the U.S. Preventive Services Task Force favoring annual screening with LDCT in current or former heavy smokers between 55 and 80 years old.
The recommendation sparked concerns about the practicability of implementing large-scale lung cancer screening, which Dr. Kinsinger and her colleagues’ study seemed to underscore. For example, “creating electronic tools to capture the necessary clinical data in real time … proved to be difficult, even with the VHA’s highly regarded electronic medical record,” the investigators wrote. A key measure used in the screening program – cigarette pack-years – was “not fully captured” in the system’s EMR.
The investigators also noted that if the eligibility criteria used in the pilot program were applied to the VHA nationwide, about 900,000 patients would be eligible for LDCT screening, and that fewer than 60% of patients in this study had consented. That meant that “accurately identifying these patients and discussing with them the benefits and harms of [screening] will take significant effort for primary care teams,” the researchers noted.
In addition, the required follow-up “may stress the capacity” of radiology and pulmonology services, the study authors cautioned.
Finally, “primary care will need to be involved in deciding which incidental findings need further evaluation,” they wrote. “These clinical efforts will require coordination and communication among clinical services and between patients and staff, and dedicated coordinators will need to be hired.”
The investigators noted that their findings might not be generalizable to non-VHA health care systems. The experience of the VHA, “owing to its central organizational structure, may represent a best-case scenario,” they wrote.
The Veterans Health Administration funded the study. Two of its coauthors reported commercial conflicts of interest; one of those disclosed a grant application to the Bristol-Myers Squibb Foundation related to lung cancer screening.
A comprehensive lung cancer screening program carried out at Veterans Health Administration hospitals was taxing to implement and revealed a large number of patients with results requiring follow-up, though only 1.5% had cancers.
Investigators at eight VHA hospitals, led by Linda S. Kinsinger, MD, of the VHA’s National Center for Health Promotion and Disease Prevention in Durham, N.C., looked at records from about 93,000 primary care patients and identified 4,246 eligible for screening, based on age, medical history, and smoking history (JAMA Intern Med. 2017 Jan 30. doi: 10.1001/jamainternmed.2016.9022).
Approximately 58% of the eligible patients consented, and 2,106 underwent screening with low-dose computed tomography (LDCT). The mean age of patients was 65 years, and 96% of patients were male.
Nearly 60% of patients screened (1,257) had nodules, 1,184 patients (56.2%) required tracking, and 31 patients (1.5%) had lung cancer.
The pilot study was developed in response to a 2013 recommendation from the U.S. Preventive Services Task Force favoring annual screening with LDCT in current or former heavy smokers between 55 and 80 years old.
The recommendation sparked concerns about the practicability of implementing large-scale lung cancer screening, which Dr. Kinsinger and her colleagues’ study seemed to underscore. For example, “creating electronic tools to capture the necessary clinical data in real time … proved to be difficult, even with the VHA’s highly regarded electronic medical record,” the investigators wrote. A key measure used in the screening program – cigarette pack-years – was “not fully captured” in the system’s EMR.
The investigators also noted that if the eligibility criteria used in the pilot program were applied to the VHA nationwide, about 900,000 patients would be eligible for LDCT screening, and that fewer than 60% of patients in this study had consented. That meant that “accurately identifying these patients and discussing with them the benefits and harms of [screening] will take significant effort for primary care teams,” the researchers noted.
In addition, the required follow-up “may stress the capacity” of radiology and pulmonology services, the study authors cautioned.
Finally, “primary care will need to be involved in deciding which incidental findings need further evaluation,” they wrote. “These clinical efforts will require coordination and communication among clinical services and between patients and staff, and dedicated coordinators will need to be hired.”
The investigators noted that their findings might not be generalizable to non-VHA health care systems. The experience of the VHA, “owing to its central organizational structure, may represent a best-case scenario,” they wrote.
The Veterans Health Administration funded the study. Two of its coauthors reported commercial conflicts of interest; one of those disclosed a grant application to the Bristol-Myers Squibb Foundation related to lung cancer screening.
A comprehensive lung cancer screening program carried out at Veterans Health Administration hospitals was taxing to implement and revealed a large number of patients with results requiring follow-up, though only 1.5% had cancers.
Investigators at eight VHA hospitals, led by Linda S. Kinsinger, MD, of the VHA’s National Center for Health Promotion and Disease Prevention in Durham, N.C., looked at records from about 93,000 primary care patients and identified 4,246 eligible for screening, based on age, medical history, and smoking history (JAMA Intern Med. 2017 Jan 30. doi: 10.1001/jamainternmed.2016.9022).
Approximately 58% of the eligible patients consented, and 2,106 underwent screening with low-dose computed tomography (LDCT). The mean age of patients was 65 years, and 96% of patients were male.
Nearly 60% of patients screened (1,257) had nodules, 1,184 patients (56.2%) required tracking, and 31 patients (1.5%) had lung cancer.
The pilot study was developed in response to a 2013 recommendation from the U.S. Preventive Services Task Force favoring annual screening with LDCT in current or former heavy smokers between 55 and 80 years old.
The recommendation sparked concerns about the practicability of implementing large-scale lung cancer screening, which Dr. Kinsinger and her colleagues’ study seemed to underscore. For example, “creating electronic tools to capture the necessary clinical data in real time … proved to be difficult, even with the VHA’s highly regarded electronic medical record,” the investigators wrote. A key measure used in the screening program – cigarette pack-years – was “not fully captured” in the system’s EMR.
The investigators also noted that if the eligibility criteria used in the pilot program were applied to the VHA nationwide, about 900,000 patients would be eligible for LDCT screening, and that fewer than 60% of patients in this study had consented. That meant that “accurately identifying these patients and discussing with them the benefits and harms of [screening] will take significant effort for primary care teams,” the researchers noted.
In addition, the required follow-up “may stress the capacity” of radiology and pulmonology services, the study authors cautioned.
Finally, “primary care will need to be involved in deciding which incidental findings need further evaluation,” they wrote. “These clinical efforts will require coordination and communication among clinical services and between patients and staff, and dedicated coordinators will need to be hired.”
The investigators noted that their findings might not be generalizable to non-VHA health care systems. The experience of the VHA, “owing to its central organizational structure, may represent a best-case scenario,” they wrote.
The Veterans Health Administration funded the study. Two of its coauthors reported commercial conflicts of interest; one of those disclosed a grant application to the Bristol-Myers Squibb Foundation related to lung cancer screening.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Comprehensive lung cancer screening is complex to implement in hospital primary care settings and may trigger resource-intensive follow-up.
Major finding: Of more than 2,000 patients screened, nearly 60% were positive for nodules, though only 1.5% had cancer.
Data source: A pilot study in 4,246 eligible primary care patients at eight Veterans Health Administration hospitals; 2,106 were screened using low-dose computed tomography.
Disclosures: The Veterans Health Administration funded the study. Two of its coauthors reported commercial conflicts of interest; one of those disclosed a grant application to the Bristol-Myers Squibb Foundation related to lung cancer screening.
Nivolumab effective in PD-L1–deficient lung cancers
VIENNA – The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.
“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.
A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.
Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.
In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.
CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.
In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.
The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.
Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.
The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.
In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.
The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.
Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.
The new analyses reported by Dr. Peters addressed the question of whether patients who receive nivolumab in place of docetaxel are disadvantaged during the first 3 months of treatment. The data showed that in CheckMate057 an excess of 15 patients died in the group randomized to receive nivolumab during the first 3 months on treatment, compared with the control patients treated with docetaxel. This is concerning. Ideally, we’d like to see the patients treated with immunotherapy respond right away, but it takes time for immunotherapy to have an effect.
In almost all immunotherapy studies, a high proportion of patients, often about a third, progress during the first 2-3 months on treatment. It will be important to identify these patients and try new treatment approaches such as combined immunotherapies or a combination of chemotherapy with immunotherapy.
The early excess mortality of 15 patients with nivolumab seen in CheckMate057 must be viewed in context. It represents just 5% of patients randomized to receive nivolumab, and hence this finding should not influence clinical practice. Nivolumab treatment produced a very strong treatment benefit overall during follow-up at 12 and 18 months, compared with docetaxel in this study.
Immunotherapy agents like nivolumab have another advantage, compared with standard chemotherapy drugs, beyond better efficacy in selected patients. Immunotherapy drugs are also generally safer than chemotherapy agents, producing fewer adverse effects. For that reason alone, immunotherapy is preferred as long as its efficacy is comparable to that of chemotherapy. Even in patients with a tumor that does not express PD-L1, and even though some non–small cell lung cancer patients will die early when put on immunotherapy, overall opinion in the clinical community favors a drug like nivolumab over chemotherapy because of its better safety.
Paul Mitchell, MD, is a medical oncologist at the Olivia Newton-John Cancer and Wellness Centre in Heidelberg, Australia. He has served on advisory boards for AstraZeneca, Roche, Boehringer-Ingelheim, BMS, Merck/MSD, Merck Serono, and Celgene; he has received honoraria from Roche and Merck; and he has received travel grants from Roche and BMS. He made these comments as the designated discussant for the report and in an interview.
VIENNA – The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.
“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.
A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.
Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.
In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.
CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – The oncologic immunotherapy drug nivolumab works by binding PD-1 receptors, but PD-L1 ligand levels in lung cancers do not predict how responsive patients are to the drug.
“While enhanced clinical activity with nivolumab correlates with increasing tumor PD-L1 expression, nivolumab-treated patients with little or no PD-L1 expression have a comparable probability of response, more durable responses, comparable overall survival, and fewer treatment-related adverse events, compared with patients treated with docetaxel,” Solange Peters, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer.
But a more detailed assessment of the survival data by Dr. Peters showed an unexpected pattern of an early hazard among the nivolumab patients. During the first 3 months on randomized treatment, 15 more patients died in the nivolumab arm than in the docetaxel arm. This quickly reversed during months 4-6 on treatment, when nine more patients died on docetaxel than on nivolumab, Dr. Peters reported. By 12 months after the onset of treatment, overall survival was 51% in the nivolumab group and 39% among those randomized to docetaxel.
A post hoc analysis showed a trend to a higher risk for death during the first 3 months of nivolumab treatment among patients with poorer prognostic features, more aggressive disease, and low or no tumor expression of PD-L1, Dr. Peters said.
Although patients with tumors with high levels of PD-L1 expression had the best response rate to nivolumab, patients with no PD-L1 expression had a response to nivolumab that was roughly equivalent to the response to docetaxel among patients randomized to chemotherapy. “Deep and durable responses were seen to nivolumab irrespective of the level of PD-L1 expression,” she said. Among patients with tumors that had a less than 1% rate of PD-L1 expression, the objective response rate was 9% with nivolumab and 15% with docetaxel. Among patients with tumors that had a PD-L1 expression rate of 1% or greater, the objective responses rate was 31% with nivolumab and 12% with docetaxel.
In a landmark analysis that excluded patients who died during the first 3 months on treatment, the pattern of responses to nivolumab and its advantage over docetaxel were similar among patients with no or low PD-L1 expression and among all patients enrolled in the study. In this landmark analysis, the hazard ratio for death after 3 months was reduced with nivolumab treatment by 34% among patients with no or low PD-L1 expression and by 31% in the entire study population, Dr. Peters reported.
CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: When tumors had at least 1% PD-L1 expression, objective response rates were 31% with nivolumab and 12% with docetaxel.
Data source: CheckMate057, a pivotal trial of nivolumab that enrolled 592 patients with advanced, nonsquamous non–small cell lung cancer.
Disclosures: CheckMate057 was funded by Bristol-Myers Squibb, the company that markets nivolumab (Opdivo). Dr. Peters has been a consultant to Bristol-Myers Squibb and to several other drug companies.
Deferring RT for brain mets in EGFR-mutated NSCLC shortens survival
Deferring radiotherapy to administer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.
Upfront therapy using EGFR TKIs such as erlotinib has been proposed as a way to avoid radiotherapy altogether in this patient population, or to at least defer it and any related toxicities until intracranial disease progresses, said William J. Magnuson, MD, of Yale University, New Haven, Conn., and his associates.
To assess the advantages and disadvantages of upfront EGFR TKIs vs. initial radiotherapy, the researchers pooled survival data for 351 patients treated at six academic medical centers during 2008-2015. A total of 131 (37%) received upfront EGFR TKIs followed by stereotactic radiosurgery or whole-brain radiotherapy when the brain metastases progressed, 120 (34%) received whole-brain radiotherapy followed by EGFR TKIs, and 100 (29%) received stereotactic radiosurgery followed by EGFR TKIs. These patients were followed for a median of 22 months.
Median overall survival was 25 months for upfront EGFR TKIs, compared with 30 months for initial whole-brain radiotherapy and 46 months for initial stereotactic radiosurgery. At 2 years, overall survival rates for the three study groups were 51%, 62%, and 78%, respectively. Both forms of initial radiotherapy were associated with improved overall survival relative to EGFR TKIs, with a hazard ratio of 0.39 for stereotactic radiosurgery and a hazard ratio of 0.70 for whole-brain irradiation.
This survival advantage was even more pronounced in the subgroup of patients who had more favorable prognostic features at baseline. These patients had a median overall survival of 64 months if they received radiotherapy followed by EGFR TKIs, compared with only 32 months if EGFR TKIs were taken before radiotherapy, the investigators said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144).
These findings have the potential to change clinical practice, but prospective randomized data to confirm the results are urgently needed. “Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain stereotactic radiosurgery followed by systemic therapy,” Dr. Magnuson and his associates said.
No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.
The findings of Magnuson et al. suggest that initial brain radiotherapy, especially stereotactic radiosurgery, is critical for patients who have EGFR-mutated NSCLC with brain metastases.
However, prospective studies are needed to confirm these results, and outcomes other than survival – including quality of life and neurocognitive function – must be addressed. The authors were unable to assess these outcomes in their pooled retrospective analysis.
In addition, potentially synergetic cognitive toxicities caused by combined or sequential therapies are still unclear, and are especially important for patients who do achieve long-term survival.
Lin Zhou, MD, and associates are at West China Hospital and Sichuan University, Chengdu, China. Dr. Zhou reported having no relevant financial disclosures; one of Dr. Zhou’s associates reported having ties to AstraZeneca. Hoffman-La Roche, Eli Lilly, Pfizer, Elekta, and Varian Medical Systems. Dr. Zhou and associates made these remarks in an editorial accompanying Dr. Magnuson’s report (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.5706).
The findings of Magnuson et al. suggest that initial brain radiotherapy, especially stereotactic radiosurgery, is critical for patients who have EGFR-mutated NSCLC with brain metastases.
However, prospective studies are needed to confirm these results, and outcomes other than survival – including quality of life and neurocognitive function – must be addressed. The authors were unable to assess these outcomes in their pooled retrospective analysis.
In addition, potentially synergetic cognitive toxicities caused by combined or sequential therapies are still unclear, and are especially important for patients who do achieve long-term survival.
Lin Zhou, MD, and associates are at West China Hospital and Sichuan University, Chengdu, China. Dr. Zhou reported having no relevant financial disclosures; one of Dr. Zhou’s associates reported having ties to AstraZeneca. Hoffman-La Roche, Eli Lilly, Pfizer, Elekta, and Varian Medical Systems. Dr. Zhou and associates made these remarks in an editorial accompanying Dr. Magnuson’s report (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.5706).
The findings of Magnuson et al. suggest that initial brain radiotherapy, especially stereotactic radiosurgery, is critical for patients who have EGFR-mutated NSCLC with brain metastases.
However, prospective studies are needed to confirm these results, and outcomes other than survival – including quality of life and neurocognitive function – must be addressed. The authors were unable to assess these outcomes in their pooled retrospective analysis.
In addition, potentially synergetic cognitive toxicities caused by combined or sequential therapies are still unclear, and are especially important for patients who do achieve long-term survival.
Lin Zhou, MD, and associates are at West China Hospital and Sichuan University, Chengdu, China. Dr. Zhou reported having no relevant financial disclosures; one of Dr. Zhou’s associates reported having ties to AstraZeneca. Hoffman-La Roche, Eli Lilly, Pfizer, Elekta, and Varian Medical Systems. Dr. Zhou and associates made these remarks in an editorial accompanying Dr. Magnuson’s report (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.71.5706).
Deferring radiotherapy to administer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.
Upfront therapy using EGFR TKIs such as erlotinib has been proposed as a way to avoid radiotherapy altogether in this patient population, or to at least defer it and any related toxicities until intracranial disease progresses, said William J. Magnuson, MD, of Yale University, New Haven, Conn., and his associates.
To assess the advantages and disadvantages of upfront EGFR TKIs vs. initial radiotherapy, the researchers pooled survival data for 351 patients treated at six academic medical centers during 2008-2015. A total of 131 (37%) received upfront EGFR TKIs followed by stereotactic radiosurgery or whole-brain radiotherapy when the brain metastases progressed, 120 (34%) received whole-brain radiotherapy followed by EGFR TKIs, and 100 (29%) received stereotactic radiosurgery followed by EGFR TKIs. These patients were followed for a median of 22 months.
Median overall survival was 25 months for upfront EGFR TKIs, compared with 30 months for initial whole-brain radiotherapy and 46 months for initial stereotactic radiosurgery. At 2 years, overall survival rates for the three study groups were 51%, 62%, and 78%, respectively. Both forms of initial radiotherapy were associated with improved overall survival relative to EGFR TKIs, with a hazard ratio of 0.39 for stereotactic radiosurgery and a hazard ratio of 0.70 for whole-brain irradiation.
This survival advantage was even more pronounced in the subgroup of patients who had more favorable prognostic features at baseline. These patients had a median overall survival of 64 months if they received radiotherapy followed by EGFR TKIs, compared with only 32 months if EGFR TKIs were taken before radiotherapy, the investigators said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144).
These findings have the potential to change clinical practice, but prospective randomized data to confirm the results are urgently needed. “Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain stereotactic radiosurgery followed by systemic therapy,” Dr. Magnuson and his associates said.
No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.
Deferring radiotherapy to administer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.
Upfront therapy using EGFR TKIs such as erlotinib has been proposed as a way to avoid radiotherapy altogether in this patient population, or to at least defer it and any related toxicities until intracranial disease progresses, said William J. Magnuson, MD, of Yale University, New Haven, Conn., and his associates.
To assess the advantages and disadvantages of upfront EGFR TKIs vs. initial radiotherapy, the researchers pooled survival data for 351 patients treated at six academic medical centers during 2008-2015. A total of 131 (37%) received upfront EGFR TKIs followed by stereotactic radiosurgery or whole-brain radiotherapy when the brain metastases progressed, 120 (34%) received whole-brain radiotherapy followed by EGFR TKIs, and 100 (29%) received stereotactic radiosurgery followed by EGFR TKIs. These patients were followed for a median of 22 months.
Median overall survival was 25 months for upfront EGFR TKIs, compared with 30 months for initial whole-brain radiotherapy and 46 months for initial stereotactic radiosurgery. At 2 years, overall survival rates for the three study groups were 51%, 62%, and 78%, respectively. Both forms of initial radiotherapy were associated with improved overall survival relative to EGFR TKIs, with a hazard ratio of 0.39 for stereotactic radiosurgery and a hazard ratio of 0.70 for whole-brain irradiation.
This survival advantage was even more pronounced in the subgroup of patients who had more favorable prognostic features at baseline. These patients had a median overall survival of 64 months if they received radiotherapy followed by EGFR TKIs, compared with only 32 months if EGFR TKIs were taken before radiotherapy, the investigators said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144).
These findings have the potential to change clinical practice, but prospective randomized data to confirm the results are urgently needed. “Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain stereotactic radiosurgery followed by systemic therapy,” Dr. Magnuson and his associates said.
No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Deferring radiotherapy to administer EGFR tyrosine kinase inhibitors first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer.
Major finding: At 2 years, overall survival rates were 51% with upfront EGFR TKIs, 62% with initial whole-brain radiotherapy, and 78% with stereotactic radiosurgery.
Data source: A retrospective multicenter pooled analysis of survival data for 351 patients with NSCLC brain metastases followed for a median of 22 months.
Disclosures: No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.
Cardiac events after NSCLC radiotherapy occur early
Cardiac events are “relatively common,” affecting 23% of patients, and occur earlier than previously thought following radiotherapy for non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.
Radiation-associated cardiac toxicity has long been recognized in patients treated for other thoracic cancers, but the conventional wisdom has been that it isn’t a consideration in patients with stage III NSCLC because “there are few long-term survivors to experience toxicity, given the typically long latency of radiotherapy-associated heart injury and the poor prognosis” of this cancer. However, the findings “challenge the perception that minimizing heart dose is not important in the treatment of patients with stage III NSCLC,” said Kyle Wang, MD, of University of North Carolina Hospitals, Chapel Hill, and his associates.
“Our data support minimization of heart radiation exposure whenever possible to doses lower than commonly recommended in patients with stage III NSCLC, to reduce risks of [cardiac] toxicity,” they noted.
Dr. Wang and his associates performed a retrospective post hoc analysis of data pooled from six prospective phase I and II trials that the University of North Carolina was involved in between 1996 and 2009. The studies assessed both dose-escalated radiotherapy and various chemotherapeutic regimens in 112 patients who were followed for a median of 8.8 years (range, 2.3-17.3 years). All the patients received induction chemotherapy, 90% received concurrent chemotherapy, and 25% received consolidation chemotherapy.
A total of 26 patients (23%) had at least one symptomatic cardiac event following radiotherapy: pericardial effusion (7 patients), MI (5 patients), unstable angina (3 patients), pericarditis (2 patients), significant arrhythmia (12 patients), and heart failure (1 patient). After the data were adjusted to account for competing risks of death, the 2-year rate of symptomatic cardiac toxicity was 10% and the 4-year rate was 18%. The first adverse cardiac event occurred at a median of 26 months (range, 1-84 months).
The risk of cardiac toxicities rose with increasing radiation exposure: At 2 years, the rate of cardiac events was 4% for those exposed to less than 10 Gy, 7% for those exposed to 10-20 Gy, and 21% for those exposed to greater than 20 Gy. At 4 years, those rates were 4%, 13%, and 41%, respectively. Patients whose hearts were exposed to greater than 20 Gy had a significantly higher rate of cardiac events than did those exposed to less than 10 Gy (HR, 5.47) or to 10-20 Gy (HR, 2.76).
Even though the prognosis may be poor in patients with stage III NSCLC, “they generally receive higher heart doses and may also have more comorbidities and smoking history, thus increasing risk and perhaps shortening the latency between radiotherapy and resultant heart disease,” Dr. Wang and his associates said (J Clin Oncol. 2017 Jan 23 [doi: 10.1200/JCO.2016.70.0229]).
“In our opinion, tumor coverage should rarely be compromised to meet a heart dose constraint. However, it would be reasonable to try to limit heart mean dose to less than 20 Gy (lower if possible) on the basis of the high event rate we observed in patients exceeding this dose (21% at 2 years and 41% at 4 years). Sophisticated radiation treatment planning techniques (e.g., [intensity-modulated radiation therapy]) and charged-particle therapy with protons or carbon ions may provide increased flexibility to generate more conformal treatment plans and reduce heart dose, which could potentially improve the clinical outcomes in patients with stage III NSCLC,” they added.
This is the first report to clearly associate radiation doses with clinically significant cardiac events in patients with locally advanced NSCLC treated with modern radiotherapy techniques, and it suggests that these events happen much earlier than conventionally believed.
Perhaps cardiac risk didn’t matter so much when, historically, the life expectancy of this patient population was only 2 years. But given the improvements in survival over the last 2 decades, together with the findings of Wang et al., the era of indiscriminate irradiation to the heart should end.
Charles B. Simone II, MD, is at the University of Maryland Medical Center, Baltimore. He reported having no relevant financial disclosures. Dr. Simone made these remarks in an editorial accompanying Dr. Wang’s report (J Clin Oncol. 2017 January 23 [doi: 10.1200/JCO.2016.71.5581]).
This is the first report to clearly associate radiation doses with clinically significant cardiac events in patients with locally advanced NSCLC treated with modern radiotherapy techniques, and it suggests that these events happen much earlier than conventionally believed.
Perhaps cardiac risk didn’t matter so much when, historically, the life expectancy of this patient population was only 2 years. But given the improvements in survival over the last 2 decades, together with the findings of Wang et al., the era of indiscriminate irradiation to the heart should end.
Charles B. Simone II, MD, is at the University of Maryland Medical Center, Baltimore. He reported having no relevant financial disclosures. Dr. Simone made these remarks in an editorial accompanying Dr. Wang’s report (J Clin Oncol. 2017 January 23 [doi: 10.1200/JCO.2016.71.5581]).
This is the first report to clearly associate radiation doses with clinically significant cardiac events in patients with locally advanced NSCLC treated with modern radiotherapy techniques, and it suggests that these events happen much earlier than conventionally believed.
Perhaps cardiac risk didn’t matter so much when, historically, the life expectancy of this patient population was only 2 years. But given the improvements in survival over the last 2 decades, together with the findings of Wang et al., the era of indiscriminate irradiation to the heart should end.
Charles B. Simone II, MD, is at the University of Maryland Medical Center, Baltimore. He reported having no relevant financial disclosures. Dr. Simone made these remarks in an editorial accompanying Dr. Wang’s report (J Clin Oncol. 2017 January 23 [doi: 10.1200/JCO.2016.71.5581]).
Cardiac events are “relatively common,” affecting 23% of patients, and occur earlier than previously thought following radiotherapy for non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.
Radiation-associated cardiac toxicity has long been recognized in patients treated for other thoracic cancers, but the conventional wisdom has been that it isn’t a consideration in patients with stage III NSCLC because “there are few long-term survivors to experience toxicity, given the typically long latency of radiotherapy-associated heart injury and the poor prognosis” of this cancer. However, the findings “challenge the perception that minimizing heart dose is not important in the treatment of patients with stage III NSCLC,” said Kyle Wang, MD, of University of North Carolina Hospitals, Chapel Hill, and his associates.
“Our data support minimization of heart radiation exposure whenever possible to doses lower than commonly recommended in patients with stage III NSCLC, to reduce risks of [cardiac] toxicity,” they noted.
Dr. Wang and his associates performed a retrospective post hoc analysis of data pooled from six prospective phase I and II trials that the University of North Carolina was involved in between 1996 and 2009. The studies assessed both dose-escalated radiotherapy and various chemotherapeutic regimens in 112 patients who were followed for a median of 8.8 years (range, 2.3-17.3 years). All the patients received induction chemotherapy, 90% received concurrent chemotherapy, and 25% received consolidation chemotherapy.
A total of 26 patients (23%) had at least one symptomatic cardiac event following radiotherapy: pericardial effusion (7 patients), MI (5 patients), unstable angina (3 patients), pericarditis (2 patients), significant arrhythmia (12 patients), and heart failure (1 patient). After the data were adjusted to account for competing risks of death, the 2-year rate of symptomatic cardiac toxicity was 10% and the 4-year rate was 18%. The first adverse cardiac event occurred at a median of 26 months (range, 1-84 months).
The risk of cardiac toxicities rose with increasing radiation exposure: At 2 years, the rate of cardiac events was 4% for those exposed to less than 10 Gy, 7% for those exposed to 10-20 Gy, and 21% for those exposed to greater than 20 Gy. At 4 years, those rates were 4%, 13%, and 41%, respectively. Patients whose hearts were exposed to greater than 20 Gy had a significantly higher rate of cardiac events than did those exposed to less than 10 Gy (HR, 5.47) or to 10-20 Gy (HR, 2.76).
Even though the prognosis may be poor in patients with stage III NSCLC, “they generally receive higher heart doses and may also have more comorbidities and smoking history, thus increasing risk and perhaps shortening the latency between radiotherapy and resultant heart disease,” Dr. Wang and his associates said (J Clin Oncol. 2017 Jan 23 [doi: 10.1200/JCO.2016.70.0229]).
“In our opinion, tumor coverage should rarely be compromised to meet a heart dose constraint. However, it would be reasonable to try to limit heart mean dose to less than 20 Gy (lower if possible) on the basis of the high event rate we observed in patients exceeding this dose (21% at 2 years and 41% at 4 years). Sophisticated radiation treatment planning techniques (e.g., [intensity-modulated radiation therapy]) and charged-particle therapy with protons or carbon ions may provide increased flexibility to generate more conformal treatment plans and reduce heart dose, which could potentially improve the clinical outcomes in patients with stage III NSCLC,” they added.
Cardiac events are “relatively common,” affecting 23% of patients, and occur earlier than previously thought following radiotherapy for non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.
Radiation-associated cardiac toxicity has long been recognized in patients treated for other thoracic cancers, but the conventional wisdom has been that it isn’t a consideration in patients with stage III NSCLC because “there are few long-term survivors to experience toxicity, given the typically long latency of radiotherapy-associated heart injury and the poor prognosis” of this cancer. However, the findings “challenge the perception that minimizing heart dose is not important in the treatment of patients with stage III NSCLC,” said Kyle Wang, MD, of University of North Carolina Hospitals, Chapel Hill, and his associates.
“Our data support minimization of heart radiation exposure whenever possible to doses lower than commonly recommended in patients with stage III NSCLC, to reduce risks of [cardiac] toxicity,” they noted.
Dr. Wang and his associates performed a retrospective post hoc analysis of data pooled from six prospective phase I and II trials that the University of North Carolina was involved in between 1996 and 2009. The studies assessed both dose-escalated radiotherapy and various chemotherapeutic regimens in 112 patients who were followed for a median of 8.8 years (range, 2.3-17.3 years). All the patients received induction chemotherapy, 90% received concurrent chemotherapy, and 25% received consolidation chemotherapy.
A total of 26 patients (23%) had at least one symptomatic cardiac event following radiotherapy: pericardial effusion (7 patients), MI (5 patients), unstable angina (3 patients), pericarditis (2 patients), significant arrhythmia (12 patients), and heart failure (1 patient). After the data were adjusted to account for competing risks of death, the 2-year rate of symptomatic cardiac toxicity was 10% and the 4-year rate was 18%. The first adverse cardiac event occurred at a median of 26 months (range, 1-84 months).
The risk of cardiac toxicities rose with increasing radiation exposure: At 2 years, the rate of cardiac events was 4% for those exposed to less than 10 Gy, 7% for those exposed to 10-20 Gy, and 21% for those exposed to greater than 20 Gy. At 4 years, those rates were 4%, 13%, and 41%, respectively. Patients whose hearts were exposed to greater than 20 Gy had a significantly higher rate of cardiac events than did those exposed to less than 10 Gy (HR, 5.47) or to 10-20 Gy (HR, 2.76).
Even though the prognosis may be poor in patients with stage III NSCLC, “they generally receive higher heart doses and may also have more comorbidities and smoking history, thus increasing risk and perhaps shortening the latency between radiotherapy and resultant heart disease,” Dr. Wang and his associates said (J Clin Oncol. 2017 Jan 23 [doi: 10.1200/JCO.2016.70.0229]).
“In our opinion, tumor coverage should rarely be compromised to meet a heart dose constraint. However, it would be reasonable to try to limit heart mean dose to less than 20 Gy (lower if possible) on the basis of the high event rate we observed in patients exceeding this dose (21% at 2 years and 41% at 4 years). Sophisticated radiation treatment planning techniques (e.g., [intensity-modulated radiation therapy]) and charged-particle therapy with protons or carbon ions may provide increased flexibility to generate more conformal treatment plans and reduce heart dose, which could potentially improve the clinical outcomes in patients with stage III NSCLC,” they added.
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Cardiac events are “relatively common” and occur earlier than previously thought following radiotherapy for NSCLC.
Major finding: Following radiotherapy, 26 of 112 patients (23%) had at least one symptomatic cardiac event: pericardial effusion (7 patients), MI (5 patients), unstable angina (3 patients), pericarditis (2 patients), significant arrhythmia (12 patients), and heart failure (1 patient).
Data source: A retrospective post hoc analysis of data from six phase I and II trials involving 112 patients who received radiotherapy for stage-III NSCLC during 1996-2009.
Disclosures: This study was supported in part by the National Institutes of Health. Dr. Wang reported having no relevant financial disclosures; his associates disclosed ties to La Jolla Pharmaceutical, Vision RT, Medtronic, Novartis, Elekta, Morphomics, Accuray, and Varian Medical Systems.
Age and disease stage predict long-term survival in elderly lung cancer patients
AT THE STS ANNUAL MEETING
HOUSTON – Although certain medical factors predict long-term survival in patients over age 65 years with lung cancer, advanced age and disease stage are especially strong predictors, results from a large analysis of national data demonstrated.
The findings, which were presented by Mark Onaitis, MD, at the annual meeting of the Society of Thoracic Surgeons, come from a novel effort to pair Medicare data with files from the STS General Thoracic Surgery Database (GTSD).
For the current study, he and his associates linked GTSD data to Medicare data on 29,899 patients who underwent lung cancer resection from 2002 to 2013. They used Cox proportional hazards modeling to create a long-term survival model and used statistically significant univariate factors and known clinical predictors of outcome to perform variable selection.
Dr. Onaitis reported that the median age of patients was 73 years and that 52% were female. Of the 29,899 patients, 805 had a missing pathologic stage. Of the 29,094 patients not missing a pathologic stage, 69% were stage I, 18% stage II, 11% stage III, and 2% stage IV. Two-thirds of patients (66%) underwent lobectomy, followed by wedge resection (17%), segmentectomy (7%), bilobectomy (3%), pneumonectomy (3%), and sleeve lobectomy (1%). A thoracoscopic approach was performed in nearly half of resections (47%).
Cox analysis revealed the following strong negative predictors of long-term survival: having stage III or IV-V disease (hazard ratio, 1.23 and 1.37, respectively), being age 70-74 (HR, 1.19), 75-80 (HR, 1.40), or 80 and older (HR, 1.90).
After controlling for disease stage, the following procedures were associated with increased hazard of death, compared with lobectomy: wedge resection (HR, 1.22), segmentectomy (HR, 1.10), bilobectomy (HR, 1.30), and pneumonectomy (HR, 1.58). In addition, video-assisted thoracoscopic surgery was associated with improved long-term survival, compared with thoracotomy (HR, 0.86).
“Given the large number of patients and the excellent quality of the data, it was not surprising that age and stage and known medical conditions affect long-term survival,” Dr. Onaitis commented. “The deleterious effects of sublobar operations and open [as opposed to thoracoscopic or VATS] approach were more pronounced than expected.”
Other modifiable predictive factors include being a past or current smoker (HR, 1.35 and HR, 1.54, respectively) and having a body mass index below 18.5 kg/m2 (HR, 1.58).
Dr. Onaitis acknowledged certain limitations of the study, including its retrospective design. “Because the study involves linkage of STS data to Medicare data, the findings may not be applicable to patients less than 65 years of age,” he added. He reported having no financial disclosures.
AT THE STS ANNUAL MEETING
HOUSTON – Although certain medical factors predict long-term survival in patients over age 65 years with lung cancer, advanced age and disease stage are especially strong predictors, results from a large analysis of national data demonstrated.
The findings, which were presented by Mark Onaitis, MD, at the annual meeting of the Society of Thoracic Surgeons, come from a novel effort to pair Medicare data with files from the STS General Thoracic Surgery Database (GTSD).
For the current study, he and his associates linked GTSD data to Medicare data on 29,899 patients who underwent lung cancer resection from 2002 to 2013. They used Cox proportional hazards modeling to create a long-term survival model and used statistically significant univariate factors and known clinical predictors of outcome to perform variable selection.
Dr. Onaitis reported that the median age of patients was 73 years and that 52% were female. Of the 29,899 patients, 805 had a missing pathologic stage. Of the 29,094 patients not missing a pathologic stage, 69% were stage I, 18% stage II, 11% stage III, and 2% stage IV. Two-thirds of patients (66%) underwent lobectomy, followed by wedge resection (17%), segmentectomy (7%), bilobectomy (3%), pneumonectomy (3%), and sleeve lobectomy (1%). A thoracoscopic approach was performed in nearly half of resections (47%).
Cox analysis revealed the following strong negative predictors of long-term survival: having stage III or IV-V disease (hazard ratio, 1.23 and 1.37, respectively), being age 70-74 (HR, 1.19), 75-80 (HR, 1.40), or 80 and older (HR, 1.90).
After controlling for disease stage, the following procedures were associated with increased hazard of death, compared with lobectomy: wedge resection (HR, 1.22), segmentectomy (HR, 1.10), bilobectomy (HR, 1.30), and pneumonectomy (HR, 1.58). In addition, video-assisted thoracoscopic surgery was associated with improved long-term survival, compared with thoracotomy (HR, 0.86).
“Given the large number of patients and the excellent quality of the data, it was not surprising that age and stage and known medical conditions affect long-term survival,” Dr. Onaitis commented. “The deleterious effects of sublobar operations and open [as opposed to thoracoscopic or VATS] approach were more pronounced than expected.”
Other modifiable predictive factors include being a past or current smoker (HR, 1.35 and HR, 1.54, respectively) and having a body mass index below 18.5 kg/m2 (HR, 1.58).
Dr. Onaitis acknowledged certain limitations of the study, including its retrospective design. “Because the study involves linkage of STS data to Medicare data, the findings may not be applicable to patients less than 65 years of age,” he added. He reported having no financial disclosures.
AT THE STS ANNUAL MEETING
HOUSTON – Although certain medical factors predict long-term survival in patients over age 65 years with lung cancer, advanced age and disease stage are especially strong predictors, results from a large analysis of national data demonstrated.
The findings, which were presented by Mark Onaitis, MD, at the annual meeting of the Society of Thoracic Surgeons, come from a novel effort to pair Medicare data with files from the STS General Thoracic Surgery Database (GTSD).
For the current study, he and his associates linked GTSD data to Medicare data on 29,899 patients who underwent lung cancer resection from 2002 to 2013. They used Cox proportional hazards modeling to create a long-term survival model and used statistically significant univariate factors and known clinical predictors of outcome to perform variable selection.
Dr. Onaitis reported that the median age of patients was 73 years and that 52% were female. Of the 29,899 patients, 805 had a missing pathologic stage. Of the 29,094 patients not missing a pathologic stage, 69% were stage I, 18% stage II, 11% stage III, and 2% stage IV. Two-thirds of patients (66%) underwent lobectomy, followed by wedge resection (17%), segmentectomy (7%), bilobectomy (3%), pneumonectomy (3%), and sleeve lobectomy (1%). A thoracoscopic approach was performed in nearly half of resections (47%).
Cox analysis revealed the following strong negative predictors of long-term survival: having stage III or IV-V disease (hazard ratio, 1.23 and 1.37, respectively), being age 70-74 (HR, 1.19), 75-80 (HR, 1.40), or 80 and older (HR, 1.90).
After controlling for disease stage, the following procedures were associated with increased hazard of death, compared with lobectomy: wedge resection (HR, 1.22), segmentectomy (HR, 1.10), bilobectomy (HR, 1.30), and pneumonectomy (HR, 1.58). In addition, video-assisted thoracoscopic surgery was associated with improved long-term survival, compared with thoracotomy (HR, 0.86).
“Given the large number of patients and the excellent quality of the data, it was not surprising that age and stage and known medical conditions affect long-term survival,” Dr. Onaitis commented. “The deleterious effects of sublobar operations and open [as opposed to thoracoscopic or VATS] approach were more pronounced than expected.”
Other modifiable predictive factors include being a past or current smoker (HR, 1.35 and HR, 1.54, respectively) and having a body mass index below 18.5 kg/m2 (HR, 1.58).
Dr. Onaitis acknowledged certain limitations of the study, including its retrospective design. “Because the study involves linkage of STS data to Medicare data, the findings may not be applicable to patients less than 65 years of age,” he added. He reported having no financial disclosures.
Key clinical point:
Major finding: Strong negative predictors of long-term survival included having stage III or IV-V disease (HR, 1.23 and 1.37, respectively), being age 70-74 (HR, 1.19), 75-80 (HR, 1.40), or 80 and older (HR, 1.90).
Data source: A retrospective analysis of 29,899 patients over age 65 who underwent lung cancer resection from 2002 to 2013.
Disclosures: Dr. Onaitis reported having no financial disclosures.
Survey finds link between e-cigarette use and high-risk behaviors
High school students who use electronic vapor products (EVPs), whether alone or in combination with cigarette smoking, are more likely to engage in violence, substance abuse, and other high-risk behaviors, compared with nonusers, according to the results of a national survey.
“Given that EVPs are relatively new to the U.S. marketplace, little is known about the use of these products in the context of other health behaviors, which can persist throughout life and contribute to significant morbidity and mortality during adolescence and adulthood,” Zewditu Demissie, PhD, and her associates wrote in a study published online in the Jan. 23, 2017, issue of Pediatrics. They went on to note that to date, “studies on the association between EVPs and health-risk behaviors among adolescents and young adults has been limited to examining the associations between e-cigarette and substance use. These studies have found that use of e-cigarettes was associated with alcohol use, binge drinking, and marijuana use.”
Of the 15,624 respondents, 74% reported that they did not smoke cigarettes or use EVPs, while 3% smoked cigarettes only, 16% used EVPs only, and 8% used both cigarettes and EVPs.
Compared with nonusers, cigarette-only smokers, EVP-only users, and dual users were significantly more likely to:
• Engage in a physical fight (prevalence ratio range, 1.7-2.9).
• Attempt suicide (PR range, 1.9-4.0).
• Currently drink alcohol (PR range, 2.6-3.3).
• Currently use marijuana (PR range, 3.5-5.2).
• Report nonmedical use of prescription drugs (PR range, 2.3-4.1).
• Be currently sexually active (PR range, 1.9-2.3).
“Engaging in health-risk behaviors did not generally differ between EVP-only users and cigarette-only smokers,” the researchers wrote. “However, cigarette-only smokers were significantly more likely than EVP-only users to attempt suicide, ever use synthetic marijuana, have four or more lifetime sexual partners, drink soda three or more times/day, and be physically active less than 7 days in the 7 days before the survey.”
Dr. Demissie and her associates concluded that the findings “underscore the importance of comprehensive efforts to address health-risk behaviors among adolescents, including prevention strategies focused on all forms of tobacco use, including EVPs. Additionally, educational and counseling efforts focusing on the harms associated with adolescent tobacco use, including EVPs, are critical.”
They acknowledged certain limitations of the study, including its observational design and the fact that Youth Risk Behavior Survey data are self-reported.
The investigators reported having no relevant financial disclosures.
“Recent longitudinal research has provided an unpleasant surprise: Among initial nonsmokers, those who use e-cigarettes are more likely to start smoking combustible cigarettes. This puts a somewhat different light on the situation. If e-cigarettes are without risk, it does not matter much if they attract new users. Being related to smoking onset, however, puts a behavioral risk into the picture. The finding of associations with other health-risk behaviors augments concern because, as the authors note, the odds of experiencing poor health increase with the addition of each unhealthy behavior. And importantly, Demissie et al. show that among adolescent smokers, those who use e-cigarettes actually smoke more frequently, an effect that is contrary to the hopes of harm reduction advocates and has now been found internationally.
“Are e-cigarettes going to replace traditional cigarettes, or are they operating to recruit a new audience of adolescents to tobacco products? Our wish is for the former. But at present the empirical evidence looks more like the latter. We need surveillance and mechanism research to understand what e-cigarettes will mean for youth risk status. However, there is enough evidence now to advocate programs for educating teenagers about e-cigarettes.”
Thomas A. Wills, PhD., is with the Cancer Prevention and Control Program at the University of Hawaii Cancer Center, Honolulu. His views are excerpted from a commentary published online in response to the study by Dr. Demissie et al. (Pediatrics. 2017 Jan 23. doi: 10.1542/peds.2016-3736). This work was supported by grants from the National Cancer Institute. Dr. Wills reported having no relevant financial disclosures.
“Recent longitudinal research has provided an unpleasant surprise: Among initial nonsmokers, those who use e-cigarettes are more likely to start smoking combustible cigarettes. This puts a somewhat different light on the situation. If e-cigarettes are without risk, it does not matter much if they attract new users. Being related to smoking onset, however, puts a behavioral risk into the picture. The finding of associations with other health-risk behaviors augments concern because, as the authors note, the odds of experiencing poor health increase with the addition of each unhealthy behavior. And importantly, Demissie et al. show that among adolescent smokers, those who use e-cigarettes actually smoke more frequently, an effect that is contrary to the hopes of harm reduction advocates and has now been found internationally.
“Are e-cigarettes going to replace traditional cigarettes, or are they operating to recruit a new audience of adolescents to tobacco products? Our wish is for the former. But at present the empirical evidence looks more like the latter. We need surveillance and mechanism research to understand what e-cigarettes will mean for youth risk status. However, there is enough evidence now to advocate programs for educating teenagers about e-cigarettes.”
Thomas A. Wills, PhD., is with the Cancer Prevention and Control Program at the University of Hawaii Cancer Center, Honolulu. His views are excerpted from a commentary published online in response to the study by Dr. Demissie et al. (Pediatrics. 2017 Jan 23. doi: 10.1542/peds.2016-3736). This work was supported by grants from the National Cancer Institute. Dr. Wills reported having no relevant financial disclosures.
“Recent longitudinal research has provided an unpleasant surprise: Among initial nonsmokers, those who use e-cigarettes are more likely to start smoking combustible cigarettes. This puts a somewhat different light on the situation. If e-cigarettes are without risk, it does not matter much if they attract new users. Being related to smoking onset, however, puts a behavioral risk into the picture. The finding of associations with other health-risk behaviors augments concern because, as the authors note, the odds of experiencing poor health increase with the addition of each unhealthy behavior. And importantly, Demissie et al. show that among adolescent smokers, those who use e-cigarettes actually smoke more frequently, an effect that is contrary to the hopes of harm reduction advocates and has now been found internationally.
“Are e-cigarettes going to replace traditional cigarettes, or are they operating to recruit a new audience of adolescents to tobacco products? Our wish is for the former. But at present the empirical evidence looks more like the latter. We need surveillance and mechanism research to understand what e-cigarettes will mean for youth risk status. However, there is enough evidence now to advocate programs for educating teenagers about e-cigarettes.”
Thomas A. Wills, PhD., is with the Cancer Prevention and Control Program at the University of Hawaii Cancer Center, Honolulu. His views are excerpted from a commentary published online in response to the study by Dr. Demissie et al. (Pediatrics. 2017 Jan 23. doi: 10.1542/peds.2016-3736). This work was supported by grants from the National Cancer Institute. Dr. Wills reported having no relevant financial disclosures.
High school students who use electronic vapor products (EVPs), whether alone or in combination with cigarette smoking, are more likely to engage in violence, substance abuse, and other high-risk behaviors, compared with nonusers, according to the results of a national survey.
“Given that EVPs are relatively new to the U.S. marketplace, little is known about the use of these products in the context of other health behaviors, which can persist throughout life and contribute to significant morbidity and mortality during adolescence and adulthood,” Zewditu Demissie, PhD, and her associates wrote in a study published online in the Jan. 23, 2017, issue of Pediatrics. They went on to note that to date, “studies on the association between EVPs and health-risk behaviors among adolescents and young adults has been limited to examining the associations between e-cigarette and substance use. These studies have found that use of e-cigarettes was associated with alcohol use, binge drinking, and marijuana use.”
Of the 15,624 respondents, 74% reported that they did not smoke cigarettes or use EVPs, while 3% smoked cigarettes only, 16% used EVPs only, and 8% used both cigarettes and EVPs.
Compared with nonusers, cigarette-only smokers, EVP-only users, and dual users were significantly more likely to:
• Engage in a physical fight (prevalence ratio range, 1.7-2.9).
• Attempt suicide (PR range, 1.9-4.0).
• Currently drink alcohol (PR range, 2.6-3.3).
• Currently use marijuana (PR range, 3.5-5.2).
• Report nonmedical use of prescription drugs (PR range, 2.3-4.1).
• Be currently sexually active (PR range, 1.9-2.3).
“Engaging in health-risk behaviors did not generally differ between EVP-only users and cigarette-only smokers,” the researchers wrote. “However, cigarette-only smokers were significantly more likely than EVP-only users to attempt suicide, ever use synthetic marijuana, have four or more lifetime sexual partners, drink soda three or more times/day, and be physically active less than 7 days in the 7 days before the survey.”
Dr. Demissie and her associates concluded that the findings “underscore the importance of comprehensive efforts to address health-risk behaviors among adolescents, including prevention strategies focused on all forms of tobacco use, including EVPs. Additionally, educational and counseling efforts focusing on the harms associated with adolescent tobacco use, including EVPs, are critical.”
They acknowledged certain limitations of the study, including its observational design and the fact that Youth Risk Behavior Survey data are self-reported.
The investigators reported having no relevant financial disclosures.
High school students who use electronic vapor products (EVPs), whether alone or in combination with cigarette smoking, are more likely to engage in violence, substance abuse, and other high-risk behaviors, compared with nonusers, according to the results of a national survey.
“Given that EVPs are relatively new to the U.S. marketplace, little is known about the use of these products in the context of other health behaviors, which can persist throughout life and contribute to significant morbidity and mortality during adolescence and adulthood,” Zewditu Demissie, PhD, and her associates wrote in a study published online in the Jan. 23, 2017, issue of Pediatrics. They went on to note that to date, “studies on the association between EVPs and health-risk behaviors among adolescents and young adults has been limited to examining the associations between e-cigarette and substance use. These studies have found that use of e-cigarettes was associated with alcohol use, binge drinking, and marijuana use.”
Of the 15,624 respondents, 74% reported that they did not smoke cigarettes or use EVPs, while 3% smoked cigarettes only, 16% used EVPs only, and 8% used both cigarettes and EVPs.
Compared with nonusers, cigarette-only smokers, EVP-only users, and dual users were significantly more likely to:
• Engage in a physical fight (prevalence ratio range, 1.7-2.9).
• Attempt suicide (PR range, 1.9-4.0).
• Currently drink alcohol (PR range, 2.6-3.3).
• Currently use marijuana (PR range, 3.5-5.2).
• Report nonmedical use of prescription drugs (PR range, 2.3-4.1).
• Be currently sexually active (PR range, 1.9-2.3).
“Engaging in health-risk behaviors did not generally differ between EVP-only users and cigarette-only smokers,” the researchers wrote. “However, cigarette-only smokers were significantly more likely than EVP-only users to attempt suicide, ever use synthetic marijuana, have four or more lifetime sexual partners, drink soda three or more times/day, and be physically active less than 7 days in the 7 days before the survey.”
Dr. Demissie and her associates concluded that the findings “underscore the importance of comprehensive efforts to address health-risk behaviors among adolescents, including prevention strategies focused on all forms of tobacco use, including EVPs. Additionally, educational and counseling efforts focusing on the harms associated with adolescent tobacco use, including EVPs, are critical.”
They acknowledged certain limitations of the study, including its observational design and the fact that Youth Risk Behavior Survey data are self-reported.
The investigators reported having no relevant financial disclosures.
FROM PEDIATRICS
Key clinical point:
Major finding: Compared with nonusers, cigarette-only smokers, electronic vapor products–only users, and dual users were significantly more likely to engage in a physical fight (prevalence ratio range, 1.7-2.3), to currently use marijuana (PR range, 3.5-5.2), and to be currently sexually active (PR range, 1.9-2.3).
Data source: An analysis of responses from 15,624 high school students who completed the 2015 national Youth Risk Behavior Survey.
Disclosures: The researchers reported having no relevant financial disclosures.
Sleeve lobectomy appears better than pneumonectomy for NSCLC
Guidelines that recommend sleeve lobectomy as a means of avoiding pneumonectomy for lung cancer have been based on a limited retrospective series, but a large series drawn from a nationwide database in France has confirmed the preference for sleeve lobectomy because it leads to higher rates of survival, despite an increased risk of postoperative pulmonary complications.
“Whenever it is technically possible, surgeons must perform sleeve lobectomy to provide more long-term survival benefits to patients, even with the risk of more postoperative pulmonary complications,” said Pierre-Benoit Pagès, MD, PhD, and his coauthors in the January 2017 issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:184-95). Dr. Pagès is with the department of thoracic and cardiovascular surgery at the University Hospital Center Dijon (France) and Bocage Hospital.
Three-year overall survival was 71.9% for the sleeve lobectomy group vs. 60.8% for the pneumonectomy group. Three-year disease-free survival was 46.4% for the sleeve lobectomy group and 31.6% for the pneumonectomy group. In addition, compared with the sleeve lobectomy group, the pneumonectomy group had an increased risk of recurrence by matching (hazard ratio, 1.49; 95% CI, 1.1-2).
The researchers performed a propensity-matched analysis that favored sleeve lobectomy for early overall and disease-free survival, but the weighted analysis did not. Patients in the sleeve lobectomy group vs. the pneumonectomy group were younger (60.9 years vs. 61.9), had higher body mass index (25.6 vs. 25.1), had higher average forced expiratory volume (74.1% vs. 62.9%), and had lower American Society of Anesthesiologists scores (73.7% with scores of 1 and 2 vs. 70.8%). Sleeve lobectomy patients also were more likely to have right-sided surgery (69.6% vs. 41%) and squamous cell carcinoma (54.6% vs. 48.3%), and lower T and N stages (T1 and T2, 60.5% vs. 40.6%; N0, 40.9% vs. 26.2%).
Overall mortality after surgery was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group, but propensity scoring showed far fewer postoperative pulmonary complications in the pneumonectomy group, with an odds ratio of 0.4, Dr. Pagès and his coauthors said. However, with other significant complications – arrhythmia, bronchopleural fistula, empyema, and hemorrhage – pneumonectomy had a propensity-matched odds ratio ranging from 1.6 to 7. “We found no significant difference regarding postoperative mortality in the sleeve lobectomy and pneumonectomy groups, whatever the statistical method used,” Dr. Pagès and his coauthors wrote.
The investigators had no financial relationships to disclose.
The study by Dr. Pagès and his colleagues is unique in the field of surgery for non–small cell lung cancer in that it drew on a nationwide database using data from 103 centers, Betty C. Tong, MD, MHS, of Duke University Medical Center, Durham, said in her invited commentary (J Thorac Cardiovasc Surg. 2017;153:196). “These results are likely as close to real life as possible,” she said.
She acknowledged that no prospective, randomized controlled trials have compared sleeve lobectomy to pneumonectomy, but she added, “it is unlikely that such a trial could be successfully executed.” The 5:1 ratio of patients having pneumonectomy vs. sleeve lobectomy in this study is similar to findings from the Society of Thoracic Surgeons General Thoracic Surgery database (J Thorac Cardiovasc Surg. 2008;132:247-54), Dr. Tong pointed out, “and likely reflects the fact that sleeve lobectomy can be technically more difficult to perform.”
The findings of the French Society of Thoracic and Cardiovascular Surgery group “should strongly encourage thoracic surgeons to perform pneumonectomy as sparingly as possible,” and consider sleeve lobectomy the standard for patients with central tumors, Dr. Tong said.
She had no financial relationships to disclose.
The study by Dr. Pagès and his colleagues is unique in the field of surgery for non–small cell lung cancer in that it drew on a nationwide database using data from 103 centers, Betty C. Tong, MD, MHS, of Duke University Medical Center, Durham, said in her invited commentary (J Thorac Cardiovasc Surg. 2017;153:196). “These results are likely as close to real life as possible,” she said.
She acknowledged that no prospective, randomized controlled trials have compared sleeve lobectomy to pneumonectomy, but she added, “it is unlikely that such a trial could be successfully executed.” The 5:1 ratio of patients having pneumonectomy vs. sleeve lobectomy in this study is similar to findings from the Society of Thoracic Surgeons General Thoracic Surgery database (J Thorac Cardiovasc Surg. 2008;132:247-54), Dr. Tong pointed out, “and likely reflects the fact that sleeve lobectomy can be technically more difficult to perform.”
The findings of the French Society of Thoracic and Cardiovascular Surgery group “should strongly encourage thoracic surgeons to perform pneumonectomy as sparingly as possible,” and consider sleeve lobectomy the standard for patients with central tumors, Dr. Tong said.
She had no financial relationships to disclose.
The study by Dr. Pagès and his colleagues is unique in the field of surgery for non–small cell lung cancer in that it drew on a nationwide database using data from 103 centers, Betty C. Tong, MD, MHS, of Duke University Medical Center, Durham, said in her invited commentary (J Thorac Cardiovasc Surg. 2017;153:196). “These results are likely as close to real life as possible,” she said.
She acknowledged that no prospective, randomized controlled trials have compared sleeve lobectomy to pneumonectomy, but she added, “it is unlikely that such a trial could be successfully executed.” The 5:1 ratio of patients having pneumonectomy vs. sleeve lobectomy in this study is similar to findings from the Society of Thoracic Surgeons General Thoracic Surgery database (J Thorac Cardiovasc Surg. 2008;132:247-54), Dr. Tong pointed out, “and likely reflects the fact that sleeve lobectomy can be technically more difficult to perform.”
The findings of the French Society of Thoracic and Cardiovascular Surgery group “should strongly encourage thoracic surgeons to perform pneumonectomy as sparingly as possible,” and consider sleeve lobectomy the standard for patients with central tumors, Dr. Tong said.
She had no financial relationships to disclose.
Guidelines that recommend sleeve lobectomy as a means of avoiding pneumonectomy for lung cancer have been based on a limited retrospective series, but a large series drawn from a nationwide database in France has confirmed the preference for sleeve lobectomy because it leads to higher rates of survival, despite an increased risk of postoperative pulmonary complications.
“Whenever it is technically possible, surgeons must perform sleeve lobectomy to provide more long-term survival benefits to patients, even with the risk of more postoperative pulmonary complications,” said Pierre-Benoit Pagès, MD, PhD, and his coauthors in the January 2017 issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:184-95). Dr. Pagès is with the department of thoracic and cardiovascular surgery at the University Hospital Center Dijon (France) and Bocage Hospital.
Three-year overall survival was 71.9% for the sleeve lobectomy group vs. 60.8% for the pneumonectomy group. Three-year disease-free survival was 46.4% for the sleeve lobectomy group and 31.6% for the pneumonectomy group. In addition, compared with the sleeve lobectomy group, the pneumonectomy group had an increased risk of recurrence by matching (hazard ratio, 1.49; 95% CI, 1.1-2).
The researchers performed a propensity-matched analysis that favored sleeve lobectomy for early overall and disease-free survival, but the weighted analysis did not. Patients in the sleeve lobectomy group vs. the pneumonectomy group were younger (60.9 years vs. 61.9), had higher body mass index (25.6 vs. 25.1), had higher average forced expiratory volume (74.1% vs. 62.9%), and had lower American Society of Anesthesiologists scores (73.7% with scores of 1 and 2 vs. 70.8%). Sleeve lobectomy patients also were more likely to have right-sided surgery (69.6% vs. 41%) and squamous cell carcinoma (54.6% vs. 48.3%), and lower T and N stages (T1 and T2, 60.5% vs. 40.6%; N0, 40.9% vs. 26.2%).
Overall mortality after surgery was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group, but propensity scoring showed far fewer postoperative pulmonary complications in the pneumonectomy group, with an odds ratio of 0.4, Dr. Pagès and his coauthors said. However, with other significant complications – arrhythmia, bronchopleural fistula, empyema, and hemorrhage – pneumonectomy had a propensity-matched odds ratio ranging from 1.6 to 7. “We found no significant difference regarding postoperative mortality in the sleeve lobectomy and pneumonectomy groups, whatever the statistical method used,” Dr. Pagès and his coauthors wrote.
The investigators had no financial relationships to disclose.
Guidelines that recommend sleeve lobectomy as a means of avoiding pneumonectomy for lung cancer have been based on a limited retrospective series, but a large series drawn from a nationwide database in France has confirmed the preference for sleeve lobectomy because it leads to higher rates of survival, despite an increased risk of postoperative pulmonary complications.
“Whenever it is technically possible, surgeons must perform sleeve lobectomy to provide more long-term survival benefits to patients, even with the risk of more postoperative pulmonary complications,” said Pierre-Benoit Pagès, MD, PhD, and his coauthors in the January 2017 issue of the Journal of Thoracic and Cardiovascular Surgery (2017;153:184-95). Dr. Pagès is with the department of thoracic and cardiovascular surgery at the University Hospital Center Dijon (France) and Bocage Hospital.
Three-year overall survival was 71.9% for the sleeve lobectomy group vs. 60.8% for the pneumonectomy group. Three-year disease-free survival was 46.4% for the sleeve lobectomy group and 31.6% for the pneumonectomy group. In addition, compared with the sleeve lobectomy group, the pneumonectomy group had an increased risk of recurrence by matching (hazard ratio, 1.49; 95% CI, 1.1-2).
The researchers performed a propensity-matched analysis that favored sleeve lobectomy for early overall and disease-free survival, but the weighted analysis did not. Patients in the sleeve lobectomy group vs. the pneumonectomy group were younger (60.9 years vs. 61.9), had higher body mass index (25.6 vs. 25.1), had higher average forced expiratory volume (74.1% vs. 62.9%), and had lower American Society of Anesthesiologists scores (73.7% with scores of 1 and 2 vs. 70.8%). Sleeve lobectomy patients also were more likely to have right-sided surgery (69.6% vs. 41%) and squamous cell carcinoma (54.6% vs. 48.3%), and lower T and N stages (T1 and T2, 60.5% vs. 40.6%; N0, 40.9% vs. 26.2%).
Overall mortality after surgery was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group, but propensity scoring showed far fewer postoperative pulmonary complications in the pneumonectomy group, with an odds ratio of 0.4, Dr. Pagès and his coauthors said. However, with other significant complications – arrhythmia, bronchopleural fistula, empyema, and hemorrhage – pneumonectomy had a propensity-matched odds ratio ranging from 1.6 to 7. “We found no significant difference regarding postoperative mortality in the sleeve lobectomy and pneumonectomy groups, whatever the statistical method used,” Dr. Pagès and his coauthors wrote.
The investigators had no financial relationships to disclose.
Key clinical point: Sleeve lobectomy for non–small cell lung cancer may lead to higher rates of overall and disease-free survival vs. pneumonectomy.
Major finding: Overall postoperative mortality was 5% in the sleeve lobectomy group vs. 5.9% in the pneumonectomy group.
Data source: An analysis of 941 sleeve lobectomy and 5,318 pneumonectomy procedures from 2005 to 2014 in the nationwide French database Epithor.
Disclosures: Dr. Pagès has received research grants from the Nuovo-Soldati Foundation for Cancer Research and the French Society of Thoracic and Cardiovascular Surgery, on whose behalf the study was performed. Dr. Pagès and his coauthors had no financial relationships to disclose.
PD-L1 testing in NSCLC patients shows high concordance
VIENNA – Several different tests for PD-L1 levels in tumor cells of patients with metastatic non–small cell lung cancer showed high concordance when run at seven French centers, boosting confidence in the clinical utility of this testing to guide first-line pembrolizumab treatment of patients with this cancer.
Among 27 laboratory-developed tests for PD-L1 (programmed death–ligand 1) levels in tumor cells that used any one of three prespecified testing platforms (made by Dako, Ventana, or Leica), 14 (52%) had “similar” concordance when compared with reference assays, Julien Adam, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer. “These results will provide the basis for making national recommendations for PD-L1 testing in patients with non–small cell lung cancer [NSCLC]” in France, added Dr. Adam, a pathologist at Gustave Roussy Cancer Center in Paris. “We expect to produce recommendations by the second half of 2017.”
Although the results came entirely from French centers, the results will also likely influence U.S. practice, predicted Shirish M. Gadgeel, MD, a thoracic oncologist at the Karmanos Cancer Institute in Detroit. The approval pembrolizumab (Keytruda) received from the Food and Drug Administration in October specified that patients with metastatic NSCLC had to show PD-L1 expression in the tumor using a FDA-approved test to receive pembrolizumab as first-line treatment.
“Before pembrolizumab’s approval there was no incentive to do PD-L1 testing,” but now it is becoming routine, he said. “It has been challenging to U.S. laboratories to decide which platform and antibody to use. Harmonization gives us confidence that if you have a platform and appropriate antibody you should be able to use the results clinically. I think the French results can be extrapolated” to U.S. practice because the results “came from multiple labs using multiple antibodies and platforms,” Dr. Gadgeel said.
The French study arranged for PD-L1 testing of NSCLC specimens from 41 patients selected as broadly representative of PD-L1 expression levels. The seven participating centers used a Dako (three centers), Ventana (two centers), or Leica (two centers) testing platform and one of five available antibodies that bind PD-L1. Every center ran tests that depended on different antibodies, and tests occurred on both tumor cells and immune cells. In total the seven testing sites collectively performed 35 stainings on each specimen for a total of 1,435 slides. In tumor cells, the overall, weighted kappa coefficient for concordance was 0.81 for tests that used the SP263 antibody and 0.78 for those using the E1L3N antibody, both high enough to make them potential candidates for routine use, said Dr. Adam. The 28-8 and 22C3 antibodies also showed high concordance levels. In contrast, some antibodies used at certain centers produced unacceptable results with concordance coefficients of less than 0.5. The best performing antibody overall was SP263.
No test measuring PD-L1 level in immune cells had an acceptable concordance rate, Dr. Adam also reported.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
Researchers have developed several different antibodies for measuring levels of PD-L1 in tumor cells and the antibodies can be used in several different testing platforms. Although most laboratories focus on using one specific immunohistochemical platform, the overall status of real-world PD-L1 testing is messy.
In the results reported by Dr. Adam, concordance weighted kappa coefficients of 0.8 or higher show extremely good concordance, and coefficients of 0.6-0.79 show good concordance. Several of the tests and testing sites reported by Dr. Adam showed concordance coefficients within these ranges. In certain other cases the concordance coefficients were very low, which prompts concern about the reliability of these low-scoring tests. The results show that the results you see in one laboratory with a specific antibody and platform test may not always remain consistent with the same antibody and platform used elsewhere.
Michael Boyer, MD, is a professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from AstraZeneca, Bristol-Myers Squibb, Clovis, Eli Lilly, Pfizer, and Roche. He made these comments as designated discussant for the report.
Researchers have developed several different antibodies for measuring levels of PD-L1 in tumor cells and the antibodies can be used in several different testing platforms. Although most laboratories focus on using one specific immunohistochemical platform, the overall status of real-world PD-L1 testing is messy.
In the results reported by Dr. Adam, concordance weighted kappa coefficients of 0.8 or higher show extremely good concordance, and coefficients of 0.6-0.79 show good concordance. Several of the tests and testing sites reported by Dr. Adam showed concordance coefficients within these ranges. In certain other cases the concordance coefficients were very low, which prompts concern about the reliability of these low-scoring tests. The results show that the results you see in one laboratory with a specific antibody and platform test may not always remain consistent with the same antibody and platform used elsewhere.
Michael Boyer, MD, is a professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from AstraZeneca, Bristol-Myers Squibb, Clovis, Eli Lilly, Pfizer, and Roche. He made these comments as designated discussant for the report.
Researchers have developed several different antibodies for measuring levels of PD-L1 in tumor cells and the antibodies can be used in several different testing platforms. Although most laboratories focus on using one specific immunohistochemical platform, the overall status of real-world PD-L1 testing is messy.
In the results reported by Dr. Adam, concordance weighted kappa coefficients of 0.8 or higher show extremely good concordance, and coefficients of 0.6-0.79 show good concordance. Several of the tests and testing sites reported by Dr. Adam showed concordance coefficients within these ranges. In certain other cases the concordance coefficients were very low, which prompts concern about the reliability of these low-scoring tests. The results show that the results you see in one laboratory with a specific antibody and platform test may not always remain consistent with the same antibody and platform used elsewhere.
Michael Boyer, MD, is a professor of medicine at the University of Sydney and a thoracic oncologist and chief clinical officer of the Chris O’Brien Lifehouse in Sydney. He has received research support from Merck and from AstraZeneca, Bristol-Myers Squibb, Clovis, Eli Lilly, Pfizer, and Roche. He made these comments as designated discussant for the report.
VIENNA – Several different tests for PD-L1 levels in tumor cells of patients with metastatic non–small cell lung cancer showed high concordance when run at seven French centers, boosting confidence in the clinical utility of this testing to guide first-line pembrolizumab treatment of patients with this cancer.
Among 27 laboratory-developed tests for PD-L1 (programmed death–ligand 1) levels in tumor cells that used any one of three prespecified testing platforms (made by Dako, Ventana, or Leica), 14 (52%) had “similar” concordance when compared with reference assays, Julien Adam, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer. “These results will provide the basis for making national recommendations for PD-L1 testing in patients with non–small cell lung cancer [NSCLC]” in France, added Dr. Adam, a pathologist at Gustave Roussy Cancer Center in Paris. “We expect to produce recommendations by the second half of 2017.”
Although the results came entirely from French centers, the results will also likely influence U.S. practice, predicted Shirish M. Gadgeel, MD, a thoracic oncologist at the Karmanos Cancer Institute in Detroit. The approval pembrolizumab (Keytruda) received from the Food and Drug Administration in October specified that patients with metastatic NSCLC had to show PD-L1 expression in the tumor using a FDA-approved test to receive pembrolizumab as first-line treatment.
“Before pembrolizumab’s approval there was no incentive to do PD-L1 testing,” but now it is becoming routine, he said. “It has been challenging to U.S. laboratories to decide which platform and antibody to use. Harmonization gives us confidence that if you have a platform and appropriate antibody you should be able to use the results clinically. I think the French results can be extrapolated” to U.S. practice because the results “came from multiple labs using multiple antibodies and platforms,” Dr. Gadgeel said.
The French study arranged for PD-L1 testing of NSCLC specimens from 41 patients selected as broadly representative of PD-L1 expression levels. The seven participating centers used a Dako (three centers), Ventana (two centers), or Leica (two centers) testing platform and one of five available antibodies that bind PD-L1. Every center ran tests that depended on different antibodies, and tests occurred on both tumor cells and immune cells. In total the seven testing sites collectively performed 35 stainings on each specimen for a total of 1,435 slides. In tumor cells, the overall, weighted kappa coefficient for concordance was 0.81 for tests that used the SP263 antibody and 0.78 for those using the E1L3N antibody, both high enough to make them potential candidates for routine use, said Dr. Adam. The 28-8 and 22C3 antibodies also showed high concordance levels. In contrast, some antibodies used at certain centers produced unacceptable results with concordance coefficients of less than 0.5. The best performing antibody overall was SP263.
No test measuring PD-L1 level in immune cells had an acceptable concordance rate, Dr. Adam also reported.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
VIENNA – Several different tests for PD-L1 levels in tumor cells of patients with metastatic non–small cell lung cancer showed high concordance when run at seven French centers, boosting confidence in the clinical utility of this testing to guide first-line pembrolizumab treatment of patients with this cancer.
Among 27 laboratory-developed tests for PD-L1 (programmed death–ligand 1) levels in tumor cells that used any one of three prespecified testing platforms (made by Dako, Ventana, or Leica), 14 (52%) had “similar” concordance when compared with reference assays, Julien Adam, MD, said at the World Conference on Lung Cancer, sponsored by the International Association for the Study of Lung Cancer. “These results will provide the basis for making national recommendations for PD-L1 testing in patients with non–small cell lung cancer [NSCLC]” in France, added Dr. Adam, a pathologist at Gustave Roussy Cancer Center in Paris. “We expect to produce recommendations by the second half of 2017.”
Although the results came entirely from French centers, the results will also likely influence U.S. practice, predicted Shirish M. Gadgeel, MD, a thoracic oncologist at the Karmanos Cancer Institute in Detroit. The approval pembrolizumab (Keytruda) received from the Food and Drug Administration in October specified that patients with metastatic NSCLC had to show PD-L1 expression in the tumor using a FDA-approved test to receive pembrolizumab as first-line treatment.
“Before pembrolizumab’s approval there was no incentive to do PD-L1 testing,” but now it is becoming routine, he said. “It has been challenging to U.S. laboratories to decide which platform and antibody to use. Harmonization gives us confidence that if you have a platform and appropriate antibody you should be able to use the results clinically. I think the French results can be extrapolated” to U.S. practice because the results “came from multiple labs using multiple antibodies and platforms,” Dr. Gadgeel said.
The French study arranged for PD-L1 testing of NSCLC specimens from 41 patients selected as broadly representative of PD-L1 expression levels. The seven participating centers used a Dako (three centers), Ventana (two centers), or Leica (two centers) testing platform and one of five available antibodies that bind PD-L1. Every center ran tests that depended on different antibodies, and tests occurred on both tumor cells and immune cells. In total the seven testing sites collectively performed 35 stainings on each specimen for a total of 1,435 slides. In tumor cells, the overall, weighted kappa coefficient for concordance was 0.81 for tests that used the SP263 antibody and 0.78 for those using the E1L3N antibody, both high enough to make them potential candidates for routine use, said Dr. Adam. The 28-8 and 22C3 antibodies also showed high concordance levels. In contrast, some antibodies used at certain centers produced unacceptable results with concordance coefficients of less than 0.5. The best performing antibody overall was SP263.
No test measuring PD-L1 level in immune cells had an acceptable concordance rate, Dr. Adam also reported.
mzoler@frontlinemedcom.com
On Twitter @mitchelzoler
AT WCLC 2016
Key clinical point:
Major finding: The concordance weighted kappa coefficient was highest for tests using the SP263 antibody, with an average coefficient of 0.81.
Data source: Forty-one non–small cell lung cancer specimens subjected to a total of 35 different tests.
Disclosures: Funding for the study came from AstraZeneca, Bristol Myers Squibb, Merck Sharp and Dohme, and Roche. Dr. Adam has been a consultant to AstraZeneca, Bristol-Myers Squibb, HalioDx, Merck Sharp and Dohme, and Roche. Dr. Gadgeel has been a speaker on behalf of Eli Lilly, Genentech, and GlaxoSmithKline and has received research funding from AstraZeneca, Eli Lilly, and Genentech. Dr. Brahmer has served on an advisory board for Merck.
Shorter Length of Stay May Not Mean Higher Readmission Rates
Length of stay (LOS) in hospitals may drop, but it doesn’t necessarily lead to higher readmission rates, according to a study by Kyoto University researchers.
In Japan, the researchers say, acute care hospital stays are longer than in other developed countries but have shortened over the past decade—mainly due to the Diagnosis Procedure Combination Per-Diem Payment System (DPC/PDPS). Under that system, introduced in 2003, hospital reimbursements from insurers reduce as LOS increases for individual patients.
Related: Risk of Readmission After Pneumonia
Concerns that excessive reductions might worsen the quality of health care led the researchers to investigate what the last 10 years of DPC/PDPS have meant for early-stage cancer surgical patients.
They analyzed 4 years of data from 804 hospitals on 42,585 surgical patients with gastric cancer, 40,156 with lung cancer, and 15,467 with colon cancer, comparing LOS with unplanned readmissions within 30 days.
They found LOS was reduced—although slightly—by about 0.5 d/y. Mean overall LOS for gastric cancer patients dropped from 21.85 days to 19.89; for lung cancer patients, from 15.61 to 14.25; for colon cancer patients, from 18.70 to 17.18.
Related: Survival After Long-Term Residence in an Intensive Care Unit
However, unplanned emergency readmission rates remained relatively stable at about 2% or declined slightly. Readmission rates were significantly lower only for lung cancer patients; declines were not significant for the other groups.
Both preoperative and postoperative LOS also decreased during the study period. In particular, the researchers note, improvements in postoperative care may have shortened LOS. They also suggest that downward trends reflect improvements due to better medical techniques, procedure choices, and advances in clinical pathways.
Source:
Kunisawa S, Fushimi K, Imanaka Y. PLoS One. 2016;11(11): e0166269.
doi: 10.1371/journal.pone.0166269.
Length of stay (LOS) in hospitals may drop, but it doesn’t necessarily lead to higher readmission rates, according to a study by Kyoto University researchers.
In Japan, the researchers say, acute care hospital stays are longer than in other developed countries but have shortened over the past decade—mainly due to the Diagnosis Procedure Combination Per-Diem Payment System (DPC/PDPS). Under that system, introduced in 2003, hospital reimbursements from insurers reduce as LOS increases for individual patients.
Related: Risk of Readmission After Pneumonia
Concerns that excessive reductions might worsen the quality of health care led the researchers to investigate what the last 10 years of DPC/PDPS have meant for early-stage cancer surgical patients.
They analyzed 4 years of data from 804 hospitals on 42,585 surgical patients with gastric cancer, 40,156 with lung cancer, and 15,467 with colon cancer, comparing LOS with unplanned readmissions within 30 days.
They found LOS was reduced—although slightly—by about 0.5 d/y. Mean overall LOS for gastric cancer patients dropped from 21.85 days to 19.89; for lung cancer patients, from 15.61 to 14.25; for colon cancer patients, from 18.70 to 17.18.
Related: Survival After Long-Term Residence in an Intensive Care Unit
However, unplanned emergency readmission rates remained relatively stable at about 2% or declined slightly. Readmission rates were significantly lower only for lung cancer patients; declines were not significant for the other groups.
Both preoperative and postoperative LOS also decreased during the study period. In particular, the researchers note, improvements in postoperative care may have shortened LOS. They also suggest that downward trends reflect improvements due to better medical techniques, procedure choices, and advances in clinical pathways.
Source:
Kunisawa S, Fushimi K, Imanaka Y. PLoS One. 2016;11(11): e0166269.
doi: 10.1371/journal.pone.0166269.
Length of stay (LOS) in hospitals may drop, but it doesn’t necessarily lead to higher readmission rates, according to a study by Kyoto University researchers.
In Japan, the researchers say, acute care hospital stays are longer than in other developed countries but have shortened over the past decade—mainly due to the Diagnosis Procedure Combination Per-Diem Payment System (DPC/PDPS). Under that system, introduced in 2003, hospital reimbursements from insurers reduce as LOS increases for individual patients.
Related: Risk of Readmission After Pneumonia
Concerns that excessive reductions might worsen the quality of health care led the researchers to investigate what the last 10 years of DPC/PDPS have meant for early-stage cancer surgical patients.
They analyzed 4 years of data from 804 hospitals on 42,585 surgical patients with gastric cancer, 40,156 with lung cancer, and 15,467 with colon cancer, comparing LOS with unplanned readmissions within 30 days.
They found LOS was reduced—although slightly—by about 0.5 d/y. Mean overall LOS for gastric cancer patients dropped from 21.85 days to 19.89; for lung cancer patients, from 15.61 to 14.25; for colon cancer patients, from 18.70 to 17.18.
Related: Survival After Long-Term Residence in an Intensive Care Unit
However, unplanned emergency readmission rates remained relatively stable at about 2% or declined slightly. Readmission rates were significantly lower only for lung cancer patients; declines were not significant for the other groups.
Both preoperative and postoperative LOS also decreased during the study period. In particular, the researchers note, improvements in postoperative care may have shortened LOS. They also suggest that downward trends reflect improvements due to better medical techniques, procedure choices, and advances in clinical pathways.
Source:
Kunisawa S, Fushimi K, Imanaka Y. PLoS One. 2016;11(11): e0166269.
doi: 10.1371/journal.pone.0166269.