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according to Enriqueta Felip, MD, the head of thoracic and head and neck cancer unit at Vall d’Hebron Institute of Oncology, Hospital, Barcelona.
IMpower010 is the first positive randomized phase 3 study to show significant disease-free survival (DFS) improvement with adjuvant cancer immunotherapy (atezolizumab, anti–programmed death–ligand 1, and platinum-based chemotherapy) in this population, Dr. Felip said in a presentation at the 2021 European Society for Medical Oncology Congress on Sept. 20 (abstract LBA9).
High unmet need
Up to 60% of patients with stage I-III NSCLC still experience disease relapse despite having received treatment, Dr. Felip said. IMpower010 included 1,280 patients who received up to four cycles of chemotherapy (cisplatin with pemetrexed, gemcitabine, docetaxel, or vinorelbine) after completely resected stage IB-IIIA NSCLC. Patients were randomized to open label to atezolizumab (1,200 mg every 21 days for 16 cycles or best supportive care (BSC). The primary endpoint of investigator-assessed DFS in the stage II-IIIA population (n = 1,005) was stratified according to three groups: PD-L1 tumor cells of at least 1% (stage II-IIIA), all-randomized (stage II-IIIA) and intention-to-treat (stage IB-IIIA).
Median disease-free survival in PD-L1 tumor cells of at least 1% was not estimated in the atezolizumab group and was 35.3 months in the BSC group (95% CI, 29.0 to NE). In the all-randomized group, median DFS was 42.3 months in the atezolizumab group (95% CI, 36.0 to NE) and 35.3 months in the BSC group (95% CI, 30.4-46.4) with a stratified hazard ratio of 0.79 (95% CI, 0.64-0.96; P = .02). In the intent-to-treat population, median DFS was not evaluable in the atezolizumab group and 37.2 months in the BSC group (95% CI, 31.6 to NE) with a hazard ratio of 0.81 (95% CI, 0.67-0.99; P = .04).
DFS hazard ratio 0.43 in TC ≥50% group
Looking at DFS by PD-L1 status in the population with and without known EGFR/ALK+ disease, Dr. Felip said that the hazard ratio for the tumor cells of at least 50% group (n = 229) was 0.43 (95% CI, 0.27-0.68), as compared with 0.87 (95% CI, 0.60-1.26) for the tumor cells 1%-49% group. With EGFR/ALK+ patients excluded, the respective HRs were similar (0.43/0.82). Considering DFS events including only disease recurrence, disease incidence was 29.4%/44.7% in the atezolizumab and BSC groups, respectively for those with PD-L1 tumor cells of at least 1%. The same pattern of atezolizumab benefit persisted in the all-randomized and intent-to-treat groups.
An assessment according to regions of relapse (locoregional only, distant only, locoregional and distant, CNS only, second primary lung) revealed no differences in the three groups. Analysis of time from randomization to relapse revealed regional differences in the PD-L1 tumor cells of at least 1% group with a median time to any relapse of 17.6 months in the atezolizumab group and 10.9 months in the BSC group. Time from randomization to relapse was generally similar for atezolizumab and best supportive care in the all randomized and intent-to-treat groups (about 11-12 months).
“The greatest magnitude of disease-free survival benefit was observed in the PD-L1 tumor cell of at least 50% population with a hazard ratio of 0.43,” Dr. Felip said. In a post hoc analysis excluding patients with known EFGR/ALK with NSCLC, she said that hazard ratios were numerically improved in most PD-L1 subgroups. Postrelapse cancer immunotherapies were used at a higher rate in the BSC arm of the trial. “Longer-term follow-up is warranted and may reveal differences in relapse patterns and treatment options.
Playing with the immune system
Benjamin Besse, MD, director of oncology and chair of the EORTC Lung Group at Paris-Saclay University, acknowledged the disease-free survival benefit with atezolizumab in IMpower010 and underscored that adjuvant immunotherapy has been changing treatment in resected cancers across tumor types (i.e., melanoma, renal cell carcinoma, NSCLC). He voiced some concerns, including the absence of benefit in PD-L1 less than 1%, pneumonectomy and EGFRmut/ALK+ patients, and generally the potential “when you play with the immune system for there to be a dark side too.” Dr. Besse said delayed side effects in 43.2% of patients , citing a recent report of chronic, mostly grade 1-2 immune-related adverse events following (>12 weeks after discontinuation) adjuvant anti–PD-1 therapy for high-risk resected melanoma. He mentioned, however, that the rate of second primary lung tumors in the atezolizumab group (1.4%) was lower than in the BSC group (2.6%), with generally similar rates between immuno- and nonimmunotherapies in melanoma and breast cancer trials.
“IMpower 010 is the first adjuvant study establishing immune checkpoint blockade as a new standard of care. We need to cure more, not to delay relapse,” he said. The optimal population for treatment is still yet to be defined, as is the best perioperative strategy, Dr. Besse added. “If approved I would prescribe adjuvant atezolizumab ... until I see the overall survival curves.”
IMpower010 was funded by–F. Hoffmann-La Roche. Dr. Felip disclosed numerous financial interests, including having received financial support from F. Hoffmann–La Roche, AstraZeneca, Amgen, and Merck, among other pharmaceutical companies.
according to Enriqueta Felip, MD, the head of thoracic and head and neck cancer unit at Vall d’Hebron Institute of Oncology, Hospital, Barcelona.
IMpower010 is the first positive randomized phase 3 study to show significant disease-free survival (DFS) improvement with adjuvant cancer immunotherapy (atezolizumab, anti–programmed death–ligand 1, and platinum-based chemotherapy) in this population, Dr. Felip said in a presentation at the 2021 European Society for Medical Oncology Congress on Sept. 20 (abstract LBA9).
High unmet need
Up to 60% of patients with stage I-III NSCLC still experience disease relapse despite having received treatment, Dr. Felip said. IMpower010 included 1,280 patients who received up to four cycles of chemotherapy (cisplatin with pemetrexed, gemcitabine, docetaxel, or vinorelbine) after completely resected stage IB-IIIA NSCLC. Patients were randomized to open label to atezolizumab (1,200 mg every 21 days for 16 cycles or best supportive care (BSC). The primary endpoint of investigator-assessed DFS in the stage II-IIIA population (n = 1,005) was stratified according to three groups: PD-L1 tumor cells of at least 1% (stage II-IIIA), all-randomized (stage II-IIIA) and intention-to-treat (stage IB-IIIA).
Median disease-free survival in PD-L1 tumor cells of at least 1% was not estimated in the atezolizumab group and was 35.3 months in the BSC group (95% CI, 29.0 to NE). In the all-randomized group, median DFS was 42.3 months in the atezolizumab group (95% CI, 36.0 to NE) and 35.3 months in the BSC group (95% CI, 30.4-46.4) with a stratified hazard ratio of 0.79 (95% CI, 0.64-0.96; P = .02). In the intent-to-treat population, median DFS was not evaluable in the atezolizumab group and 37.2 months in the BSC group (95% CI, 31.6 to NE) with a hazard ratio of 0.81 (95% CI, 0.67-0.99; P = .04).
DFS hazard ratio 0.43 in TC ≥50% group
Looking at DFS by PD-L1 status in the population with and without known EGFR/ALK+ disease, Dr. Felip said that the hazard ratio for the tumor cells of at least 50% group (n = 229) was 0.43 (95% CI, 0.27-0.68), as compared with 0.87 (95% CI, 0.60-1.26) for the tumor cells 1%-49% group. With EGFR/ALK+ patients excluded, the respective HRs were similar (0.43/0.82). Considering DFS events including only disease recurrence, disease incidence was 29.4%/44.7% in the atezolizumab and BSC groups, respectively for those with PD-L1 tumor cells of at least 1%. The same pattern of atezolizumab benefit persisted in the all-randomized and intent-to-treat groups.
An assessment according to regions of relapse (locoregional only, distant only, locoregional and distant, CNS only, second primary lung) revealed no differences in the three groups. Analysis of time from randomization to relapse revealed regional differences in the PD-L1 tumor cells of at least 1% group with a median time to any relapse of 17.6 months in the atezolizumab group and 10.9 months in the BSC group. Time from randomization to relapse was generally similar for atezolizumab and best supportive care in the all randomized and intent-to-treat groups (about 11-12 months).
“The greatest magnitude of disease-free survival benefit was observed in the PD-L1 tumor cell of at least 50% population with a hazard ratio of 0.43,” Dr. Felip said. In a post hoc analysis excluding patients with known EFGR/ALK with NSCLC, she said that hazard ratios were numerically improved in most PD-L1 subgroups. Postrelapse cancer immunotherapies were used at a higher rate in the BSC arm of the trial. “Longer-term follow-up is warranted and may reveal differences in relapse patterns and treatment options.
Playing with the immune system
Benjamin Besse, MD, director of oncology and chair of the EORTC Lung Group at Paris-Saclay University, acknowledged the disease-free survival benefit with atezolizumab in IMpower010 and underscored that adjuvant immunotherapy has been changing treatment in resected cancers across tumor types (i.e., melanoma, renal cell carcinoma, NSCLC). He voiced some concerns, including the absence of benefit in PD-L1 less than 1%, pneumonectomy and EGFRmut/ALK+ patients, and generally the potential “when you play with the immune system for there to be a dark side too.” Dr. Besse said delayed side effects in 43.2% of patients , citing a recent report of chronic, mostly grade 1-2 immune-related adverse events following (>12 weeks after discontinuation) adjuvant anti–PD-1 therapy for high-risk resected melanoma. He mentioned, however, that the rate of second primary lung tumors in the atezolizumab group (1.4%) was lower than in the BSC group (2.6%), with generally similar rates between immuno- and nonimmunotherapies in melanoma and breast cancer trials.
“IMpower 010 is the first adjuvant study establishing immune checkpoint blockade as a new standard of care. We need to cure more, not to delay relapse,” he said. The optimal population for treatment is still yet to be defined, as is the best perioperative strategy, Dr. Besse added. “If approved I would prescribe adjuvant atezolizumab ... until I see the overall survival curves.”
IMpower010 was funded by–F. Hoffmann-La Roche. Dr. Felip disclosed numerous financial interests, including having received financial support from F. Hoffmann–La Roche, AstraZeneca, Amgen, and Merck, among other pharmaceutical companies.
according to Enriqueta Felip, MD, the head of thoracic and head and neck cancer unit at Vall d’Hebron Institute of Oncology, Hospital, Barcelona.
IMpower010 is the first positive randomized phase 3 study to show significant disease-free survival (DFS) improvement with adjuvant cancer immunotherapy (atezolizumab, anti–programmed death–ligand 1, and platinum-based chemotherapy) in this population, Dr. Felip said in a presentation at the 2021 European Society for Medical Oncology Congress on Sept. 20 (abstract LBA9).
High unmet need
Up to 60% of patients with stage I-III NSCLC still experience disease relapse despite having received treatment, Dr. Felip said. IMpower010 included 1,280 patients who received up to four cycles of chemotherapy (cisplatin with pemetrexed, gemcitabine, docetaxel, or vinorelbine) after completely resected stage IB-IIIA NSCLC. Patients were randomized to open label to atezolizumab (1,200 mg every 21 days for 16 cycles or best supportive care (BSC). The primary endpoint of investigator-assessed DFS in the stage II-IIIA population (n = 1,005) was stratified according to three groups: PD-L1 tumor cells of at least 1% (stage II-IIIA), all-randomized (stage II-IIIA) and intention-to-treat (stage IB-IIIA).
Median disease-free survival in PD-L1 tumor cells of at least 1% was not estimated in the atezolizumab group and was 35.3 months in the BSC group (95% CI, 29.0 to NE). In the all-randomized group, median DFS was 42.3 months in the atezolizumab group (95% CI, 36.0 to NE) and 35.3 months in the BSC group (95% CI, 30.4-46.4) with a stratified hazard ratio of 0.79 (95% CI, 0.64-0.96; P = .02). In the intent-to-treat population, median DFS was not evaluable in the atezolizumab group and 37.2 months in the BSC group (95% CI, 31.6 to NE) with a hazard ratio of 0.81 (95% CI, 0.67-0.99; P = .04).
DFS hazard ratio 0.43 in TC ≥50% group
Looking at DFS by PD-L1 status in the population with and without known EGFR/ALK+ disease, Dr. Felip said that the hazard ratio for the tumor cells of at least 50% group (n = 229) was 0.43 (95% CI, 0.27-0.68), as compared with 0.87 (95% CI, 0.60-1.26) for the tumor cells 1%-49% group. With EGFR/ALK+ patients excluded, the respective HRs were similar (0.43/0.82). Considering DFS events including only disease recurrence, disease incidence was 29.4%/44.7% in the atezolizumab and BSC groups, respectively for those with PD-L1 tumor cells of at least 1%. The same pattern of atezolizumab benefit persisted in the all-randomized and intent-to-treat groups.
An assessment according to regions of relapse (locoregional only, distant only, locoregional and distant, CNS only, second primary lung) revealed no differences in the three groups. Analysis of time from randomization to relapse revealed regional differences in the PD-L1 tumor cells of at least 1% group with a median time to any relapse of 17.6 months in the atezolizumab group and 10.9 months in the BSC group. Time from randomization to relapse was generally similar for atezolizumab and best supportive care in the all randomized and intent-to-treat groups (about 11-12 months).
“The greatest magnitude of disease-free survival benefit was observed in the PD-L1 tumor cell of at least 50% population with a hazard ratio of 0.43,” Dr. Felip said. In a post hoc analysis excluding patients with known EFGR/ALK with NSCLC, she said that hazard ratios were numerically improved in most PD-L1 subgroups. Postrelapse cancer immunotherapies were used at a higher rate in the BSC arm of the trial. “Longer-term follow-up is warranted and may reveal differences in relapse patterns and treatment options.
Playing with the immune system
Benjamin Besse, MD, director of oncology and chair of the EORTC Lung Group at Paris-Saclay University, acknowledged the disease-free survival benefit with atezolizumab in IMpower010 and underscored that adjuvant immunotherapy has been changing treatment in resected cancers across tumor types (i.e., melanoma, renal cell carcinoma, NSCLC). He voiced some concerns, including the absence of benefit in PD-L1 less than 1%, pneumonectomy and EGFRmut/ALK+ patients, and generally the potential “when you play with the immune system for there to be a dark side too.” Dr. Besse said delayed side effects in 43.2% of patients , citing a recent report of chronic, mostly grade 1-2 immune-related adverse events following (>12 weeks after discontinuation) adjuvant anti–PD-1 therapy for high-risk resected melanoma. He mentioned, however, that the rate of second primary lung tumors in the atezolizumab group (1.4%) was lower than in the BSC group (2.6%), with generally similar rates between immuno- and nonimmunotherapies in melanoma and breast cancer trials.
“IMpower 010 is the first adjuvant study establishing immune checkpoint blockade as a new standard of care. We need to cure more, not to delay relapse,” he said. The optimal population for treatment is still yet to be defined, as is the best perioperative strategy, Dr. Besse added. “If approved I would prescribe adjuvant atezolizumab ... until I see the overall survival curves.”
IMpower010 was funded by–F. Hoffmann-La Roche. Dr. Felip disclosed numerous financial interests, including having received financial support from F. Hoffmann–La Roche, AstraZeneca, Amgen, and Merck, among other pharmaceutical companies.
FROM ESMO 2021