First-Line Nivolumab Plus Ipilimumab With Chemotherapy Versus Chemotherapy Alone for Metastatic NSCLC in CheckMate 9LA: 3-Year Clinical Update and Outcomes in Patients With Brain Metastases or Select Somatic Mutations

Abstract

Introduction

In the phase 3 CheckMate 9LA study, nivolumab plus ipilimumab with chemotherapy prolonged overall survival (OS) versus chemotherapy alone. We report updated efficacy/safety (≥3 years' follow-up), clinical outcomes in patients with baseline brain metastases, and exploratory somatic mutation analyses.

Methods

Adults with stage IV/recurrent non–small cell lung cancer (NSCLC), no known sensitizing EGFR/ALK alterations, and Eastern Cooperative Oncology Group performance status ≤1 were randomized 1:1 to nivolumab 360 mg every 3 weeks plus ipilimumab 1 mg/kg every 6 weeks with chemotherapy (2 cycles), or chemotherapy alone (4 cycles). Assessments included OS, progression-free survival (PFS), and objective response rate. Exploratory analyses included systemic/intracranial efficacy in patients with or without baseline brain metastases, in addition to OS and PFS by KRAS, TP53, STK11, and KEAP1 somatic mutation status in patients with non-squamous NSCLC.

Results

With a minimum follow-up of 36.1 months, nivolumab plus ipilimumab with chemotherapy continued to prolong OS versus chemotherapy alone in the intent-to-treat population (median [HR; 95% CI] OS: 15.8 versus 11.0 months [0.74; 0.62–0.87]; 3-year OS: 27% versus 19%). Efficacy outcomes were improved in patients with pretreated baseline brain metastases (median [HR; 95% CI] OS: 19.3 versus 6.8 months [0.45; 0.29–0.70]; systemic PFS: 9.7 versus 4.1 months [0.44; 0.28–0.69]; intracranial PFS: 11.4 versus 4.6 months [0.42; 0.26–0.68]). A trend of OS benefit was observed in patients treated with nivolumab plus ipilimumab with chemotherapy versus chemotherapy alone, despite KRAS, TP53, and STK11 tumor mutations. Extended follow-up revealed no new safety signals.

Conclusions

With a 3-year minimum follow-up, nivolumab plus ipilimumab with 2 cycles of chemotherapy continued to demonstrate long-term, durable efficacy versus chemotherapy alone; manageable safety profile; and survival benefit in patients with or without baseline brain metastases or select somatic mutations, further supporting the regimen as first-line treatment for patients with metastatic NSCLC.