Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): A randomized, double-blind, placebo-controlled, phase 3 trial (LBA 5)

Abstract

<b>Objectives:</b> Niraparib, a potent poly(adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitor, demonstrated statistically significant improvement in progression-free survival (PFS) in advanced ovarian cancer (OC) patients (pts) with complete or partial response (CR/PR) after first-line platinum-based chemotherapy (1L CT) regardless of biomarker status in the global phase 3 PRIMA study. The PRIME study was conducted to evaluate the efficacy and safety of niraparib using an individualized starting dose as a maintenance treatment following CR/PR to 1L CT in Chinese pts with advanced OC. <b>Methods:</b> In this double-blind, placebo (PBO)-controlled, multicenter phase 3 study, pts with newly diagnosed, advanced (stage III-IV) OC (including high-grade serious or endometrioid ovarian, primary peritoneal, or fallopian tube cancer) with CR/PR to 1L CT were randomized 2:1 to niraparib or PBO once-daily. A starting dose of 200 mg once daily (QD) was used, except in pts with a baseline body weight of ≥ 77 kg and platelet count ≥ 150,000/μL who received 300 mg QD. Pts were stratified by gBRCA status (mutated [m]/non-gBRCAm), tumor HRD status (HRDpos, HRDneg [including not determined, missing] by BGI Genomics assay, receipt of neoadjuvant chemotherapy (yes/no), and best response to 1L CT (CR/PR). All randomized pts remained on assigned treatment until disease progression, unacceptable toxicity, death, withdrawal of consent, or lost to follow-up. The primary endpoint was PFS assessed by blinded independent central review, analyzed using a stratified log-rank test and a Cox proportional hazards model. The secondary endpoint included overall survival (OS). All efficacy outcome measures were analyzed based on the intention-to-treat (ITT) population. <b>Results:</b> Of the 384 randomized pts (niraparib, n=255; PBO, n=129); 125 (32.6%) were gBRCAm, 257 (66.9%) were HRd population (HRDpos/non-gBRCAm or gBRCAm) (data cutoff [DCO], 30 September 2021). The median follow-up was 27.5 months. Median PFS was significantly longer among pts who received niraparib compared with PBO (24.8 <i>vs</i> 8.3 months; hazard ratio [HR] 0.45; 95% confidence interval [CI] 0.34–0.60; <i>P</i><0.001; Figure 1). All subgroup analysis demonstrated consistent treatment benefit with HRd population (HR 0.48) and HRp (HR 0.41). OS data was immature (as of DCO, number of OS events: 65[16.9 %] occurred; HR, 0.63; 95% CI, 0.38-1.03). The most common grade ≥ 3 adverse events in niraparib arm were anemia (18.0%), neutrophil count decreased (17.3%), and platelet count decreased (14.1%), 1.6%, 1.6%, and 0.8% in placebo arm, respectively. <b>Conclusions:</b> The PRIME study is the first phase 3 study to confirm the efficacy and safety of niraparib as a single agent in Chinese pts with newly diagnosed advanced OC as 1L maintenance therapy. Pts who received niraparib had a clinically meaningful and statistically significant improvement in PFS compared to those who received PBO, regardless of biomarker status. Niraparib was well tolerated and no new safety signals were identified.Fig. 1