Niraparib plus pembrolizumab maintenance therapy shows no difference in progression-free survival for NSCLCTrial Shows Niraparib Plus Pembrolizumab Does Not Improve NSCLC Outcomes

INTRODUCTION: This randomized, double-blind, phase 3 study evaluated niraparib plus pembrolizumab as maintenance therapy for patients with advanced or metastatic NSCLC (NSCLC; ZEAL-1L, ClinicalTrials.gov identifier: NCT04475939). METHODS: Adults with advanced or metastatic squamous or nonsquamous NSCLC without a known targetable driver alteration were randomly assigned (1:1) to receive niraparib plus pembrolizumab or placebo plus pembrolizumab as maintenance therapy. Niraparib was given as a daily oral dose of 300 or 200 mg, and intravenous pembrolizumab was administered at 200 mg every 3 weeks. The primary end point was progression-free survival (PFS) by blinded independent central review in patients with a complete or partial response (CR/PR) to front-line chemotherapy combined with pembrolizumab. Hierarchical testing was performed on the primary and key secondary end points in a prespecified sequential order; formal testing was stopped if any end point failed to reach statistical significance. RESULTS: Patients comprising the intent-to-treat (ITT) population (n = 666) were randomly assigned to niraparib plus pembrolizumab (n = 331) or placebo-plus-pembrolizumab (n = 335) therapy. The median PFS for the CR/PR population (n = 200 receiving niraparib plus pembrolizumab; n = 201 receiving placebo-plus-pembrolizumab) was 5.55 months in both treatment arms (hazard ratio, 1.00; 95% confidence interval: 0.79-1.27; 1-sided p = 0.502). Key secondary end points of PFS by blinded independent central review in the ITT population, overall survival in the CR/PR and ITT populations, and time to progression in the central nervous system were not formally tested. The most common grade 3 or higher treatment-related adverse events in the niraparib plus pembrolizumab arm were hematologic (anemia, thrombocytopenia, and neutropenia). CONCLUSION: The addition of niraparib to pembrolizumab for maintenance therapy in patients with advanced or metastatic NSCLC did not result in improved efficacy; no new safety signals were detected. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT04475939.