Advertisement

First-line Nivolumab Plus Ipilimumab With Chemotherapy Versus Chemotherapy Alone for Metastatic Non–Small Cell Lung Cancer in CheckMate 9LA: 3-Year Clinical Update and Outcomes in Patients With Brain Metastases or Select Somatic Mutations

Published:October 28, 2022DOI:https://doi.org/10.1016/j.jtho.2022.10.014
      This paper is only available as a PDF. To read, Please Download here.

      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.

      Keywords

      Abbreviations:

      AE (adverse event), ALK (anaplastic lymphoma kinase), BICR (blinded independent central review), BOR (best observed response), chemo (chemotherapy), CI (confidence interval), CNS (central nervous system), CTLA-4 (cytotoxic T-lymphocyte antigen 4), DOR (duration of response), ECOG PS (Eastern Cooperative Oncology Group performance status), EGFR (epidermal growth factor receptor), HR (hazard ratio), IHC (immunohistochemistry), IMAE (immune-mediated adverse event), IPI (ipilimumab), IQR (interquartile range), NA (not applicable), NIVO (nivolumab), NR (not reached), NSQ (non-squamous), ORR (overall response rate), OS (overall survival), PD-1 (programmed death 1 receptor), PD-L1 (programmed death ligand 1), PFS (progression-free survival), Q3W (every 3 weeks), Q6W (every 6 weeks), SQ (squamous), TRAE (treatment-related adverse event)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Thoracic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect