Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1

Martin Reck, Tudor Eliade Ciuleanu, Jong Seok Lee, Michael Schenker, Bogdan Zurawski, Sang We Kim, Mauricio Mahave, Aurelia Alexandru, Solange Peters, Adam Pluzanski, Reyes Bernabe Caro, Helena Linardou, Jacobus A. Burgers, Makoto Nishio, Alex Martinez-Marti, Koichi Azuma, Rita Axelrod, Luis G. Paz-Ares, Suresh S. Ramalingam, Hossein BorghaeiKenneth J. O'Byrne, Li Li, Judith Bushong, Ravi G. Gupta, Diederik J. Grootendorst, Laura J. Eccles, Julie R. Brahmer

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Introduction: In CheckMate 227 Part 1, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with metastatic NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) expression. Here, we report post hoc exploratory systemic and intracranial efficacy outcomes and safety by baseline brain metastasis status at 5 years’ minimum follow-up. Methods: Treatment-naive adults with stage IV or recurrent NSCLC without EGFR or ALK alterations, including asymptomatic patients with treated brain metastases, were enrolled. Patients with tumor PD-L1 greater than or equal to 1% were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy; patients with tumor PD-L1 less than 1% were randomized to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy groups. Assessments included OS, systemic and intracranial progression-free survival per blinded independent central review, new brain lesion development, and safety. Brain imaging was performed at baseline (all randomized patients) and approximately every 12 weeks thereafter (patients with baseline brain metastases only). Results: Overall, 202 of 1739 randomized patients had baseline brain metastases (nivolumab plus ipilimumab: 68; chemotherapy: 66). At 61.3 months’ minimum follow-up, nivolumab plus ipilimumab prolonged OS versus chemotherapy in patients with baseline brain metastases (hazard ratio = 0.63; 95% confidence interval: 0.43–0.92) and in those without (hazard ratio = 0.76; 95% confidence interval: 0.66–0.87). In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ipilimumab (12% and 16%, respectively) than chemotherapy (0% and 6%). Fewer patients with baseline brain metastases developed new brain lesions with nivolumab plus ipilimumab (4%) versus chemotherapy (20%). No new safety signals were observed. Conclusions: With all patients off immunotherapy for more than or equal to 3 years, nivolumab plus ipilimumab continued to provide a long-term, durable survival benefit in patients with or without brain metastases. Intracranial efficacy outcomes favored nivolumab plus ipilimumab versus chemotherapy. These results further support nivolumab plus ipilimumab as an efficacious first-line treatment for patients with metastatic NSCLC, regardless of baseline brain metastasis status.

Original languageEnglish
Pages (from-to)1055-1069
Number of pages15
JournalJournal of Thoracic Oncology
Volume18
Issue number8
DOIs
StatePublished - Aug 2023

Keywords

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • B7-H1 Antigen/metabolism
  • Brain Neoplasms/drug therapy
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Humans
  • Ipilimumab/pharmacology
  • Lung Neoplasms/pathology
  • Neoplasm Recurrence, Local/drug therapy
  • Nivolumab/pharmacology

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