Treatment With Niraparib Maintenance Therapy in Patients With Newly Diagnosed Advanced Ovarian Cancer : A Phase 3 Randomized Clinical Trial

Key Points

Question

Does treatment with niraparib prolong progression-free survival in patients with newly diagnosed advanced ovarian cancer?

Finding

In the PRIME phase 3 randomized clinical trial of 384 patients with newly diagnosed advanced ovarian cancer after receiving first-line platinum-based chemotherapy, including those who underwent R0 resection at primary debulking surgery, treatment with niraparib with an individualized starting dose significantly extended progression-free survival vs placebo and reduced the risk of disease progression or death by 55%.

Meaning

The results of this randomized clinical trial support niraparib monotherapy as a standard of care after first-line platinum-based chemotherapy in a broad patient population with advanced ovarian cancer.

Abstract

Importance

The efficacy of niraparib maintenance therapy with an individualized starting dose (ISD) warrants further investigation in a broad population with newly diagnosed advanced ovarian cancer (aOC), including patients without postoperative residual disease.

Objective

To evaluate the efficacy and safety of niraparib with an ISD in a broad population with newly diagnosed aOC (R0 resection permitted).

Design, Setting, and Participants

This multicenter, randomized, double-blind, placebo-controlled, phase 3 study was conducted in China and enrolled 384 patients with newly diagnosed aOC who received primary or interval debulking surgery and responded to treatment with first-line platinum-based chemotherapy. By data cutoff (September 30, 2021), median follow-up for progression-free survival (PFS) was 27.5 (IQR, 24.7-30.4) months.

Interventions

Patients were randomized 2:1 to receive niraparib or placebo with ISD (200 mg/d for those with a body weight of <77 kg and/or platelet count of <150 ×10 ³/μL [to convert to ×10 ⁹/μL, multiply by 1] at baseline; 300 mg/d otherwise) stratified by germline BRCA variant status, tumor homologous recombination deficiency status, neoadjuvant chemotherapy, and response to first-line platinum-based chemotherapy.

Main Outcomes and Measurements

The primary end point was blinded, independent central review–assessed PFS in the intention-to-treat population.

Results

A total of 384 patients were randomized (255 niraparib [66.4%]; median [range] age, 53 [32-77] years; 129 placebo [33.6%]; median [range] age, 54 [33-77] years), and 375 (247 niraparib [65.9%], 128 placebo [34.1%]) received treatment at a dose of 200 mg per day. Median PFS with niraparib vs placebo was 24.8 vs 8.3 months (hazard ratio [HR], 0.45; 95% CI, 0.34-0.60; P < .001) in the intention-to-treat population; not reached vs 10.8 months (HR, 0.40; 95% CI, 0.23-0.68) and 19.3 vs 8.3 months (HR, 0.48; 95% CI, 0.34-0.67) in patients with and without germline BRCA variants, respectively; not reached vs 11.0 months (HR, 0.48; 95% CI, 0.34-0.68) and 16.6 vs 5.5 months (HR, 0.41; 95% CI, 0.22-0.75) in homologous recombination deficient and proficient patients, respectively; and 24.8 vs 8.3 months (HR, 0.44; 95% CI, 0.32-0.61) and 16.5 vs 8.3 months (HR, 0.27; 95% CI, 0.10-0.72) in those with optimal and suboptimal debulking, respectively. Similar proportions of niraparib-treated and placebo-treated patients (6.7% vs 5.4%) discontinued treatment due to treatment-emergent adverse events.

Conclusion and Relevance

This randomized clinical trial found that niraparib maintenance therapy prolonged PFS in patients with newly diagnosed aOC regardless of postoperative residual disease or biomarker status. The ISD was effective and safe in the first-line maintenance setting.

Trial Registration

ClinicalTrials.gov Identifier: NCT03709316

Abstract

This randomized clinical trial examines the efficacy and safety of treatment with niraparib with an individualized starting dose in Chinese patients with newly diagnosed advanced ovarian cancer.