Nivolumab plus ipilimumab with chemotherapy as first-line treatment of patients with metastatic non-small-cell lung cancer: final, 6-year outcomes from CheckMate 9LA

BACKGROUND: The phase III CheckMate 9LA study demonstrated durable overall survival (OS) benefit with nivolumab plus ipilimumab with chemotherapy versus chemotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). Here, we report final, 6-year efficacy and safety outcomes. PATIENTS AND METHODS: Treatment-naive adults with stage IV/recurrent NSCLC and no sensitizing EGFR/ALK alterations were randomized to nivolumab plus ipilimumab with chemotherapy (n = 361) or chemotherapy (n = 358). Assessments included OS, progression-free survival, objective response rate, and duration of response (DOR) in all randomized patients and subgroups, and OS by select somatic mutation status (KRAS, STK11, KEAP1, and TP53). RESULTS: With 68.6 months' minimum follow-up, nivolumab plus ipilimumab with chemotherapy demonstrated continued OS benefit versus chemotherapy (hazard ratio 0.74, 95% confidence interval 0.63-0.87, 6-year OS rates 16% versus 10%), regardless of tumor programmed death ligand 1 (PD-L1) expression (PD-L1 <1%, 20% versus 7%; PD-L1 ≥1%, 15% versus 10%) and histology (squamous, 14% versus 5%; non-squamous, 17% versus 12%). The 6-year DOR rate was 19% with nivolumab plus ipilimumab with chemotherapy; all patients in the chemotherapy arm were censored or stopped responding before this timepoint. Trends toward improved OS were observed with nivolumab plus ipilimumab with chemotherapy over chemotherapy regardless of KRAS, STK11, KEAP1, or TP53 mutation status. No new safety signals were observed. CONCLUSIONS: These final analyses demonstrate the durable, long-term OS and response benefit with first-line nivolumab plus ipilimumab with chemotherapy over chemotherapy in patients with metastatic NSCLC, regardless of tumor PD-L1 expression, histology, or select somatic mutation status, further supporting this regimen as a standard-of-care treatment option.