Treatment-Free Survival Over 6 Years of Follow-up in Patients With Metastatic NSCLC Treated With First-Line Nivolumab Plus Ipilimumab Versus Chemotherapy in CheckMate 227 Part 1.

INTRODUCTION: Treatment-free survival (TFS) characterizes periods of disease control and durable clinical benefit after treatment discontinuation in patients treated with immunotherapy. In CheckMate 227 Part 1, nivolumab plus ipilimumab reported long-term durable overall survival (OS) benefit versus chemotherapy in patients with metastatic NSCLC. Here, we report updated long-term TFS results. METHODS: This analysis included all patients randomized (tumor programmed death ligand 1 [PD-L1] expression ≥1% and <1%). TFS was estimated as the restricted-mean survival time (between Kaplan-Meier curves for time to treatment discontinuation and time to subsequent systemic therapy or death) over 6 years after randomization. TFS was further divided into periods with or without ongoing toxicity (grade 3 or greater treatment-related adverse events) and estimated over 2 and 6 years after randomization. RESULTS: At 6 years after randomization (minimum follow-up: 73.5 months [∼6.1 years]), the estimated OS rate was 20% with nivolumab plus ipilimumab versus 11% with chemotherapy; 13% versus 2% of patients were treatment free. The 6-year mean TFS was 12.2 versus 5.0 months (difference 7.2 [95% confidence interval: 5.4-9.2]), with 17% versus 7% of the 6-year period spent in TFS. The 6-year mean TFS without grade 3 or greater treatment-related adverse events was 11.6 versus 4.8 months (difference, 6.9 [95% confidence interval: 5.1-8.9]). The proportion of mean TFS time increased from 15% of a 2-year to 17% of a 6-year period with nivolumab plus ipilimumab but decreased from 14% to 7% with chemotherapy. Similar results were observed by tumor PD-L1 expression. CONCLUSIONS: Nivolumab plus ipilimumab improved TFS versus chemotherapy, regardless of tumor PD-L1 expression, supporting its use as an efficacious first-line treatment for metastatic NSCLC.