First-Line Nivolumab Plus Ipilimumab With Chemotherapy Versus Chemotherapy Alone for Metastatic NSCLC in CheckMate 9LA: 3-Year Clinical Update and Outcomes in Patients With Brain Metastases or Select Somatic Mutations |
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| Affiliation: | 1. Medical Oncology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain;2. Department of Medical Oncology, Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania;3. Department of Medical Oncology, Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Málaga, Spain;4. Department of Pneumology, Thoracic Oncology, University Hospital of Nantes and INSERM, CRCINA, Nantes, France;5. Department of Medical Oncology, SF Nectarie Oncology Center, Craiova, Romania;6. Department of Oncology, Jilin Cancer Hospital, Changchun, Jilin, People’s Republic of China;7. Department of Medical Oncology, Hospital Universitario La Fe, Valencia, Spain;8. Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan;9. Department of Oncology, Instituto Medico Rio Cuarto SA, Córdoba, Argentina;10. Medical Oncology Unit, Fundacion Arturo Lopez Perez, Santiago, Chile;11. Department of Oncology, Asklepios Lung Clinic, German Center for Lung Research, Munich-Gauting, Germany;12. Department of Oncology, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil;13. Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland;14. Department of Chemotherapy and Innovative Technologies, N.N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia;15. Department of Clinical Oncology, Instituto Oncológico de Córdoba, Córdoba, Argentina;p. Medical Oncology Service (Lung Cancer Unit), Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Barcelona, Spain;q. Department of Cancer Services, St John of God Hospital Murdoch, Perth, Australia;r. Chemotherapy Department, Ambulatorium Chemioterapii, Bydgoszcz, Poland;s. Department of Oncology, Institute of Oncology Prof Dr Alexandru Trestioreanu Bucha, Bucharest, Romania;t. Department of Medical Oncology, Instituto Jalisciense De Cancerología, Guadalajara, Mexico;u. Department of Oncology, Cancer Center of Kansas, Wichita, Kansas;v. Department of Medical Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, People’s Republic of China;w. Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, LungClinic, Grosshansdorf, Germany;x. Medical Oncology Department, Austin Hospital, Heidelberg, Victoria, Australia;y. Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, New Jersey;z. Global Drug Development, Oncology Clinical Development, Bristol Myers Squibb, Princeton, New Jersey;11. Global Medical Oncology, Bristol Myers Squibb, Princeton, New Jersey;22. Translational Sciences Oncology Imaging, Bristol Myers Squibb, Princeton, New Jersey;33. Informatics and Predictive Sciences, Bristol Myers Squibb, Princeton, New Jersey;44. Translational Medicine, Bristol Myers Squibb, Princeton, New Jersey;55. Department of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio |
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| Abstract: | IntroductionIn the phase 3 CheckMate 9LA study, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy alone. We report updated efficacy and safety (≥3 y of follow-up), clinical outcomes in patients with baseline brain metastases, and exploratory somatic mutation analyses.MethodsAdults with stage IV or recurrent NSCLC, no known sensitizing EGFR or ALK alterations, and Eastern Cooperative Oncology Group performance status less than or equal to 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 alone (four cycles). Assessments included OS, progression-free survival (PFS), and objective response rate. Exploratory analyses included systemic and intracranial efficacy in patients with or without baseline brain metastases, in addition to OS and PFS by KRAS, TP53, STK11, and KEAP1 somatic mutation status in patients with nonsquamous NSCLC.ResultsWith a minimum follow-up of 36.1 months, nivolumab plus ipilimumab with chemotherapy continued to prolong OS versus chemotherapy alone in the intent-to-treat population (median [hazard ratio; 95% confidence interval] OS: 15.8 versus 11.0 mo [0.74; 0.62–0.87]; 3-y OS: 27% versus 19%). Efficacy outcomes were improved in patients with pretreated baseline brain metastases (median [hazard ratio; 95% confidence interval] OS: 19.3 versus 6.8 mo [0.45; 0.29–0.70]; systemic PFS: 9.7 versus 4.1 mo [0.44; 0.28–0.69]; intracranial PFS: 11.4 versus 4.6 mo [0.42; 0.26–0.68]). A trend of OS benefit was observed in patients treated with nivolumab plus ipilimumab with chemotherapy versus chemotherapy alone, despite KRAS, TP53, and STK11 tumor mutations. Extended follow-up revealed no new safety signals.ConclusionsWith a 3-year minimum follow-up, nivolumab plus ipilimumab with two cycles of chemotherapy continued to have long-term, durable efficacy versus chemotherapy alone; a manageable safety profile; and survival benefit in patients with or without baseline brain metastases or select somatic mutations, further supporting the regimen as first-line treatment for patients with metastatic NSCLC. |
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| Keywords: | PD-1 checkpoint inhibitor Metastatic non–small cell lung cancer First-line Brain metastases Somatic mutations |
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