First-line Nivolumab Plus Ipilimumab With Chemotherapy Versus Chemotherapy Alone for Metastatic Non–Small Cell Lung Cancer in CheckMate 9LA: 3-Year Clinical Update and Outcomes in Patients With Brain Metastases or Select Somatic Mutations

Published:October 28, 2022DOI:
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      In the phase 3 CheckMate 9LA study, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy alone. We report updated efficacy/safety (≥3 years’ follow-up), clinical outcomes in patients with baseline brain metastases, and exploratory somatic mutation analyses.


      Adults with stage IV/recurrent non–small cell lung cancer (NSCLC), no known sensitizing EGFR/ALK alterations, and Eastern Cooperative Oncology Group performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (2 cycles), or chemotherapy alone (4 cycles). Assessments included OS, progression-free survival (PFS), and objective response rate. Exploratory analyses included systemic/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 non-squamous NSCLC.


      With 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 [HR; 95% CI] OS: 15.8 versus 11.0 months [0.74; 0.62–0.87]; 3-year OS: 27% versus 19%). Efficacy outcomes were improved in patients with pretreated baseline brain metastases (median [HR; 95% CI] OS: 19.3 versus 6.8 months [0.45; 0.29–0.70]; systemic PFS: 9.7 versus 4.1 months [0.44; 0.28–0.69]; intracranial PFS: 11.4 versus 4.6 months [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.


      With a 3-year minimum follow-up, nivolumab plus ipilimumab with 2 cycles of chemotherapy continued to demonstrate long-term, durable efficacy versus chemotherapy alone; 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.



      AE (adverse event), ALK (anaplastic lymphoma kinase), BICR (blinded independent central review), BOR (best observed response), chemo (chemotherapy), CI (confidence interval), CNS (central nervous system), CTLA-4 (cytotoxic T-lymphocyte antigen 4), DOR (duration of response), ECOG PS (Eastern Cooperative Oncology Group performance status), EGFR (epidermal growth factor receptor), HR (hazard ratio), IHC (immunohistochemistry), IMAE (immune-mediated adverse event), IPI (ipilimumab), IQR (interquartile range), NA (not applicable), NIVO (nivolumab), NR (not reached), NSQ (non-squamous), ORR (overall response rate), OS (overall survival), PD-1 (programmed death 1 receptor), PD-L1 (programmed death ligand 1), PFS (progression-free survival), Q3W (every 3 weeks), Q6W (every 6 weeks), SQ (squamous), TRAE (treatment-related adverse event)
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