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

Background: Treatment-free survival (TFS) characterizes periods of disease control and durable clinical benefit following treatment discontinuation in patients treated with immunotherapy. In CheckMate 227 Part 1, nivolumab plus ipilimumab showed 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 randomized patients (tumor 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/death) over 6-years post-randomization. TFS was further divided into periods with/without ongoing toxicity (grade ≥3 treatment-related adverse events [TRAEs]) and estimated over 2- and 6-years post-randomization.

Results: At 6-years post-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 (difference 7.2 [95% confidence interval (CI): 5.4-9.2]) months, with 17% versus 7% of the 6-year period spent in TFS. The 6-year mean TFS without grade ≥3 TRAEs was 11.6 versus 4.8 (difference, 6.9 [95% CI: 5.1-8.9]) months. The proportion of mean TFS time increased from 15% of 2-year to 17% of 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.