Niraparib Improves rPFS in Patients With mCRPC and HRR Alterations

Niraparib can improve upon first-line treatment with abiraterone acetate and prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations, a phase 3 trial suggests.

Researchers found that niraparib plus AAP prolonged radiographic progression-free survival (rPFS) when compared with AAP alone in patients with BRCA1/2 alterations or any HRR alterations.

The researchers reported these findings, from the phase 3 MAGNITUDE trial, in Annals of Oncology.

The trial (ClinicalTrials.gov Identifier: NCT03748641) included 423 patients with mCRPC who had at least 1 HRR gene alteration, including 225 patients who had BRCA1/2 alterations.

The patients were randomly assigned to receive first-line treatment with niraparib plus AAP (n=212) or AAP plus placebo (n=211). Niraparib was given at 200 mg daily, abiraterone acetate was given at 1000 mg daily, and prednisone was given at 10 mg daily.

In this second interim analysis, the median follow-up was 26.8 months for the entire HRR-positive population and 24.8 months for the BRCA1/2-positive subgroup.

Blinded independent central review showed that niraparib improved rPFS in the overall study population and in the BRCA1/2-positive subgroup. 

In the overall cohort, the median rPFS was 16.7 months in the niraparib arm and 13.7 months in the placebo arm (hazard ratio [HR], 0.76; 95% CI, 0.60-0.97; P =.0280). In the BRCA1/2-positive subgroup, the median rPFS was 19.5 months in the niraparib arm and 10.9 months in the placebo arm (HR, 0.55; 95% CI, 0.39-0.78; P =.0007).

Niraparib was associated with an improvement in time to symptomatic progression in the BRCA1/2-positive subgroup (HR, 0.54; 95% CI, 0.35-0.85; P =.0071) and the overall cohort (HR, 0.60; 95% CI, 0.42-0.84; P =.0029).

In addition, niraparib prolonged the time to initiation of cytotoxic chemotherapy in the BRCA1/2-positive subgroup (HR, 0.56; 95% CI, 0.35-0.90; P =.0152) and the overall cohort (HR, 0.67; 95% CI, 0.47-0.94; P =.0206).

On the other hand, niraparib did not improve overall survival (OS) in either group.

In the overall cohort, the median OS was 29.3 months in the niraparib arm and 32.2 months in the placebo arm (HR, 1.01; 95% CI, 0.75-1.36; P =.9480). In the BRCA1/2-positive subgroup, the median OS was 29.3 months in the niraparib arm and 28.6 months in the placebo arm (HR, 0.88; 95% CI, 0.58-1.34; P =.5505).

The safety profile in this analysis was consistent with the safety profile in the first interim analysis, according to the researchers.

The incidence of adverse events in the current analysis was 99.5% in the niraparib arm and 96.2% in the placebo arm. The most common adverse events (in the niraparib and placebo arms, respectively) were anemia (50.0% vs 22.7%), hypertension (33.0% vs 22.3%), and constipation (33.0% vs 15.6%).

Disclosures: This research was supported by Janssen Research & Development, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Chi KN, Sandhu S, Smith MR, et al. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: Second interim analysis of the randomized phase III MAGNITUDE trial. Ann Oncol. Published online July 1, 2023. doi:10.1016/j.annonc.2023.06.009

This article originally appeared on Cancer Therapy Advisor