Treatment-Switching Adjustment of Overall Survival in CheckMate 227 Part 1 Evaluating First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy for Metastatic Nonsmall Cell Lung Cancer.

Objectives: CheckMate 227 (NCT02477826) evaluated first-line nivolumab-plus-ipilimumab versus chemotherapy in patients with metastatic nonsmall cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) expression ≥ 1% or < 1% and no EGFR/ALK alterations. However, many patients randomized to chemotherapy received subsequent immunotherapy. Here, overall survival (OS) and relative OS benefit of nivolumab-plus-ipilimumab were adjusted for potential bias introduced by treatment switching.

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 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 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).