First-Line Nivolumab Plus Ipilimumab in Advanced Non-Small Cell Lung Cancer: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial

ABSTRACT Introduction In CheckMate 227, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with tumor programmed death ligand 1 (PD-L1) ≥1% (primary end point) or Methods Adults with previously untreated stage IV/recurrent NSCLC were randomized (1:1:1) to nivolumab plus ipilimumab, nivolumab, or chemotherapy (PD-L1 ≥1%); or to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 Results After 54.8 months’ median follow-up, OS remained longer with nivolumab plus ipilimumab versus chemotherapy in patients with PD-L1 ≥1% (HR 0.76; 95% CI: 0.65–0.90) and PD-L1 Conclusions At >4 years’ minimum follow-up, with all patients off immunotherapy treatment for ≥2 years, first-line nivolumab plus ipilimumab continued to demonstrate durable long-term efficacy in patients with advanced NSCLC. No new safety signals were identified. Immune-mediated AEs occurred early and resolved quickly with guidelines-based management. Discontinuation of nivolumab plus ipilimumab due to TRAEs did not have a negative impact on the long-term benefits seen in all randomized patients.