Efficacy and Safety of Niraparib as Maintenance Treatment in Patients with Extensive-Stage Small Cell Lung Cancer after First-Line Chemotherapy: A Randomized, Double-Blind, Phase 3 Study.

Abstract

INTRODUCTION\nZL-2306-005 is a randomized, double-blind, multicenter phase 3 study evaluating the efficacy and safety of niraparib, a poly(ADP-ribose) polymerase inhibitor, as first-line maintenance therapy in Chinese patients with platinum-responsive, extensive-stage small cell lung cancer (ES-SCLC).\n\n\nMETHODS\nPatients with complete/partial response (CR/PR) to standardized, platinum-based first-line chemotherapy were randomized 2:1 to receive niraparib or placebo (300 mg [baseline body weight ≥77 kg, platelet count ≥150,000/μL] or 200 mg) once daily until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) (blinded independent central review, BICR) and overall survival (OS) (sample size planned: 591 patients). Secondary endpoints included investigator-assessed PFS and safety.\n\n\nRESULTS\nZL-2306-005 was terminated early due to ES-SCLC treatment landscape changes (data cut-off: 20 Mar 2020). During July 2018-February 2020, 185 of 272 patients screened were randomized (niraparib: n=125 [CR=1, PR=124]; placebo: n=60 [CR=1, PR=59]). Median (95% confidence interval [CI]) PFS (BICR) was 1.54 months (1.41-2.69, niraparib) and 1.36 months (1.31-1.48, placebo); hazard ratio [HR]=0.66 (95% CI: 0.46-0.95; p=0.0242). Median OS was 9.92 months (9.33-13.54, niraparib) and 11.43 months (9.53-not estimable, placebo); HR=1.03 (95% CI: 0.62-1.73; p=0.9052). Median investigator-assessed PFS was 1.48 months (1.41-2.56, niraparib) and 1.41 months (1.31-2.00, placebo); HR=0.88 (95% CI: 0.61-1.26; p=0.4653). Grade ≥3 adverse events occurred in 34.4% (niraparib) and 25.0% (placebo) of patients.\n\n\nCONCLUSIONS\nZL-2306-005 did not reach primary endpoints. However, niraparib as maintenance therapy modestly improved PFS in patients with platinum-responsive ES-SCLC, with acceptable tolerability profile and no new safety signal.