Niraparib Plus Abiraterone Acetate and Prednisone Continues to Benefit Patients with HRR-Altered Metastatic Castration-Resistant Prostate Cancer

Second Interim Analysis of the Phase 3 MAGNITUDE Trial

According to the second interim analysis of the MAGNITUDE study, niraparib, a highly selective PARP-1 and PARP-2 inhibitor, plus abiraterone acetate plus prednisone (AAP) improved radiographic progression-free survival (rPFS) and other clinically relevant outcomes among patients with metastatic castration-resistant prostate cancer and homologous recombination repair alterations, especially BRCA1/2.

As Kim N Chi, MD, BC Cancer—Vancouver Center, British Columbia, Canada, and coauthors wrote, “BRCA1/2 alterations are associated with poor clinical outcomes and treatment resistance." However, they went on, "PARP inhibitors have consistently shown significant activity in patients with [metastatic castration-resistant prostate cancer] with HRR defects, especially in BRCA genes.”

In this phase 3 trial, 423 patients were randomized on a 1-to-1 basis to receive either 200 mg niraparib plus 1000 mg/10 mg AAP (experimental arm; n = 212) or placebo plus AAP (placebo arm; n = 211). Patients were prospectively identified as HRR-positive with or without BRCA1/2. The BRCA 1/2 subgroup of the experimental arm included 113 patients.

The secondary end points assessed at this interim analysis were time to symptomatic progression (defined as the earliest time to the need for orthopedic surgical intervention, need for other cancer-related procedure, need for new systemic anti-cancer treatment for pain, need for external beam radiation therapy [EBRT], or cancer-related morbid event), time to initiation of cytotoxic chemotherapy, and overall survival (OS).

At the time of the second interim analysis, the median follow-up duration was 24.8 months in the BRCA1/2 subgroup. The radiographic progression-free survival of BRCA1/2-positive patients in the experimental arm was 19.5 months, vs 10.9 months in the placebo arm (Hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.39 to 0.78; nominal P = .0007). This significant improvement was consistent with the previous interim analysis, and was also seen in the total HRR-positive population (HR = .076; 95% CI, 0.60 to 0.97; nominal P = .0280). In the experimental arm, there were also improvements in the time to symptomatic progression and time to initiation of cytotoxic chemotherapy.

Dr Chi et al concluded this trial “demonstrated improved rPFS and other clinically relevant outcomes with niraparib plus AAP in patients with BRCA1/2-altered [metastatic castration-resistant prostate cancer],” and added that this data “continue to support the use of [niraparib] plus AAP in patients with [metastatic castration-resistant prostate cancer] and select HRR gene alterations, especially BRCA1/2, and reinforce the need for genomic testing” of patients in this population.

Source:

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. 2023;34(9):772-782. doi:10.1016/jannonc2023.06.009