Long-Term Survival Outcomes With First-Line Nivolumab Plus Ipilimumab–Based Treatment in Patients With Metastatic NSCLC and Tumor Programmed Death-Ligand 1 Lower Than 1%: A Pooled Analysis

Solange Peters, Luis G. Paz-Ares, Martin Reck, David P. Carbone, Julie R. Brahmer, Hossein Borghaei, Shun Lu, Kenneth J. O'Byrne, Thomas John, Tudor Eliade Ciuleanu, Michael Schenker, Reyes Bernabe Caro, Makoto Nishio, Manuel Cobo, Jong Seok Lee, Bogdan Zurawski, Adam Pluzanski, Takekazu Aoyama, Marina Tschaika, Vipul DevasDiederik J. Grootendorst, Suresh S. Ramalingam

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: Nivolumab plus ipilimumab–based treatment regimens have shown long-term, durable efficacy benefits in patients with metastatic NSCLC. Here we report clinical outcomes from a pooled analysis of patients with metastatic NSCLC and tumor programmed death-ligand 1 (PD-L1) lower than 1% treated with first-line nivolumab plus ipilimumab with or without two cycles of chemotherapy versus up to four cycles of chemotherapy in the randomized phase 3 CheckMate 227 and CheckMate 9LA studies. Methods: Patients were aged 18 years or older and had stage IV or recurrent NSCLC with no sensitizing EGFR/ALK alterations. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety. Results: In patients with tumor PD-L1 lower than 1% in the nivolumab plus ipilimumab with or without chemotherapy (n = 322) versus chemotherapy (n = 315) arms, median OS was 17.4 versus 11.3 months, respectively, (hazard ratio [HR] = 0.64, 95% confidence interval [CI]: 0.54–0.76; 5-y OS rate, 20% versus 7%) at a median follow-up of 73.7 months. The OS benefit was observed across key subgroups, including difficult-to-treat populations such as those with baseline brain metastases (HR = 0.44, 95% CI: 0.26–0.75) or squamous NSCLC (HR = 0.51, 95% CI: 0.36–0.72). In the overall pooled population, the median PFS was 5.4 versus 4.9 months (HR = 0.72, 95% CI: 0.60–0.87; 5-y PFS rate, 9% versus 2%), the objective response rate was 29% versus 22%, and the median duration of response was 18.0 versus 4.6 months. No new safety signals were observed. Conclusion: Nivolumab plus ipilimumab with or without chemotherapy provides a long-term, durable clinical benefit in patients with metastatic NSCLC and tumor PD-L1 lower than 1%, supporting the use of this strategy as a first-line treatment option in this population with high unmet need.

Original languageEnglish
Pages (from-to)94-108
Number of pages15
JournalJournal of Thoracic Oncology
Volume20
Issue number1
DOIs
StatePublished - Jan 2025

Keywords

  • Immunotherapy
  • Ipilimumab
  • Nivolumab
  • Non–small cell lung cancer
  • PD-L1

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