Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial
Background In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatmen...
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BMJ Publishing Group
2024-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/2/e008189.full |
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| author | Enriqueta Felip David P. Carbone Martin Reck Luis Paz-Ares Yong Yuan Nan Hu Niels Reinmuth Xiaoqing Zhang Thomas John Ying Cheng Shun Lu Manuel Cobo Michael Schenker Tudor-Eliade Ciuleanu Stéphanie Bordenave Oscar Juan-Vidal Juliana Menezes Eduardo Richardet Hideaki Mizutani Bogdan Zurawski Aurelia Alexandru Javed Mahmood Tuli De Irene Santi John R. Penrod Adam Lee |
| author_facet | Enriqueta Felip David P. Carbone Martin Reck Luis Paz-Ares Yong Yuan Nan Hu Niels Reinmuth Xiaoqing Zhang Thomas John Ying Cheng Shun Lu Manuel Cobo Michael Schenker Tudor-Eliade Ciuleanu Stéphanie Bordenave Oscar Juan-Vidal Juliana Menezes Eduardo Richardet Hideaki Mizutani Bogdan Zurawski Aurelia Alexandru Javed Mahmood Tuli De Irene Santi John R. Penrod Adam Lee |
| author_sort | Enriqueta Felip |
| collection | DOAJ |
| description | Background In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy.Methods Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing EGFR/ALK alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population). Assessments included OS, progression-free survival, and objective response rate. Exploratory analyses included efficacy by tumor PD-L1 expression and histology and in patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events (TRAEs), and a treatment-switching adjustment analysis using inverse probability of censoring weighting.Results With a 47.9-month minimum follow-up for OS, nivolumab plus ipilimumab with chemotherapy continued to prolong OS over chemotherapy in all randomized patients (HR 0.74, 95% CI 0.63 to 0.87; 4-year OS rate: 21% versus 16%), regardless of tumor PD-L1 expression (HR (95% CI): PD-L1<1%, 0.66 (0.50 to 0.86) and ≥1%, 0.74 (0.60 to 0.92)) or histology (squamous, 0.64 (0.48 to 0.84) and non-squamous, 0.80 (0.66 to 0.97)). In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy due to TRAEs (n=61), the 4-year OS rate was 41%. With treatment-switching adjustment for the 36% of patients receiving subsequent immunotherapy in the chemotherapy arm, the estimated HR of nivolumab plus ipilimumab with chemotherapy versus chemotherapy was 0.66 (95% CI 0.55 to 0.80). No new safety signals were observed.Conclusions In this 4-year update, patients treated with nivolumab plus ipilimumab with chemotherapy continued to have long-term, durable efficacy benefit over chemotherapy regardless of tumor PD-L1 expression and/or histology. A greater estimated relative OS benefit was observed after adjustment for subsequent immunotherapy use in the chemotherapy arm. These results further support nivolumab plus ipilimumab with chemotherapy as a first-line treatment for patients with metastatic/recurrent NSCLC, including those with tumor PD-L1<1% or squamous histology, populations with high unmet needs. |
| format | Article |
| id | doaj-art-c372aee3045841d7bf925f1ae98c8480 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-c372aee3045841d7bf925f1ae98c84802025-02-03T10:55:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-02-0112210.1136/jitc-2023-008189Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trialEnriqueta Felip0David P. Carbone1Martin Reck2Luis Paz-Ares3Yong Yuan4Nan Hu5Niels Reinmuth6Xiaoqing Zhang7Thomas John8Ying Cheng9Shun Lu10Manuel Cobo11Michael Schenker12Tudor-Eliade Ciuleanu13Stéphanie Bordenave14Oscar Juan-Vidal15Juliana Menezes16Eduardo Richardet17Hideaki Mizutani18Bogdan Zurawski19Aurelia Alexandru20Javed Mahmood21Tuli De22Irene Santi23John R. Penrod24Adam Lee25Medical Oncology Service, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, SpainDivision of Medical Oncology and the Pelotonia Institute for Immuno-Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA4Lungenclinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany18Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, SpainGlobal Drug Development, Oncology Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USASchool of Electronics and Information Engineering, Soochow University, Suzhou, Jiangsu, ChinaDepartment of Oncology, Asklepios Lung Clinic, German Center for Lung Research, Munich-Gauting, GermanyGlobal Drug Development, Oncology Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USAMedical Oncology Department, Austin Hospital, Heidelberg, Victoria, Australia12Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China2Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China13 Medical Oncology Intercenter Unit. IBIMA, Virgen de la Victoria University Hospital Pharmacy Clinic Management Unit, Malaga, Andalucía, Spain6Policlinica Sf. Nectarie, Centrul de Oncologie, Craiova, Romania4 Department of Oncology, Oncology Institute Prof Dr Ion Chiricuta, Cluj-Napoca, RomaniaL’institut du Thorax, Nantes, France7Hospital Universitari i Politécnic La Fe de Valencia, Valencia, SpainDepartment of Oncology, Hospital Nossa Senhora da Conceição, Porto Alegre, BrazilDepartment of Clinical Oncology, IONC Instituto Oncológico de Córdoba, Córdoba, ArgentinaDepartment of Thoracic Oncology, Saitama Cancer Center, Saitama, JapanChemotherapy Department, Ambulatorium Chemioterapii, Bydgoszcz, PolandDepartment of Oncology, Institute of Oncology Prof Dr Alexandru Trestioreanu Bucha, Bucharest, RomaniaGlobal Drug Development, Oncology Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USAParexel, Billerica, Massachusetts, USAParexel, Billerica, Massachusetts, USAGlobal Drug Development, Oncology Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USAGlobal Drug Development, Oncology Clinical Development, Bristol Myers Squibb, Princeton, New Jersey, USABackground In CheckMate 9LA, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy regardless of tumor PD-L1 expression or histology. We report updated efficacy and safety in all randomized patients with a minimum 4-year follow-up and an exploratory treatment-switching adjustment analysis in all treated patients who received chemotherapy and subsequent immunotherapy.Methods Adults with stage IV/recurrent non-small cell lung cancer (NSCLC), no sensitizing EGFR/ALK alterations, and ECOG performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (two cycles) or chemotherapy (four cycles, with optional maintenance pemetrexed for the nonsquamous population). Assessments included OS, progression-free survival, and objective response rate. Exploratory analyses included efficacy by tumor PD-L1 expression and histology and in patients who discontinued nivolumab plus ipilimumab with chemotherapy due to treatment-related adverse events (TRAEs), and a treatment-switching adjustment analysis using inverse probability of censoring weighting.Results With a 47.9-month minimum follow-up for OS, nivolumab plus ipilimumab with chemotherapy continued to prolong OS over chemotherapy in all randomized patients (HR 0.74, 95% CI 0.63 to 0.87; 4-year OS rate: 21% versus 16%), regardless of tumor PD-L1 expression (HR (95% CI): PD-L1<1%, 0.66 (0.50 to 0.86) and ≥1%, 0.74 (0.60 to 0.92)) or histology (squamous, 0.64 (0.48 to 0.84) and non-squamous, 0.80 (0.66 to 0.97)). In patients who discontinued all components of nivolumab plus ipilimumab with chemotherapy due to TRAEs (n=61), the 4-year OS rate was 41%. With treatment-switching adjustment for the 36% of patients receiving subsequent immunotherapy in the chemotherapy arm, the estimated HR of nivolumab plus ipilimumab with chemotherapy versus chemotherapy was 0.66 (95% CI 0.55 to 0.80). No new safety signals were observed.Conclusions In this 4-year update, patients treated with nivolumab plus ipilimumab with chemotherapy continued to have long-term, durable efficacy benefit over chemotherapy regardless of tumor PD-L1 expression and/or histology. A greater estimated relative OS benefit was observed after adjustment for subsequent immunotherapy use in the chemotherapy arm. These results further support nivolumab plus ipilimumab with chemotherapy as a first-line treatment for patients with metastatic/recurrent NSCLC, including those with tumor PD-L1<1% or squamous histology, populations with high unmet needs.https://jitc.bmj.com/content/12/2/e008189.full |
| spellingShingle | Enriqueta Felip David P. Carbone Martin Reck Luis Paz-Ares Yong Yuan Nan Hu Niels Reinmuth Xiaoqing Zhang Thomas John Ying Cheng Shun Lu Manuel Cobo Michael Schenker Tudor-Eliade Ciuleanu Stéphanie Bordenave Oscar Juan-Vidal Juliana Menezes Eduardo Richardet Hideaki Mizutani Bogdan Zurawski Aurelia Alexandru Javed Mahmood Tuli De Irene Santi John R. Penrod Adam Lee Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial Journal for ImmunoTherapy of Cancer |
| title | Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial |
| title_full | Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial |
| title_fullStr | Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial |
| title_full_unstemmed | Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial |
| title_short | Four-year clinical update and treatment switching-adjusted outcomes with first-line nivolumab plus ipilimumab with chemotherapy for metastatic non-small cell lung cancer in the CheckMate 9LA randomized trial |
| title_sort | four year clinical update and treatment switching adjusted outcomes with first line nivolumab plus ipilimumab with chemotherapy for metastatic non small cell lung cancer in the checkmate 9la randomized trial |
| url | https://jitc.bmj.com/content/12/2/e008189.full |
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