FDA Approves Niraparib and Abiraterone Acetate Plus Prednisone for Castration-Resistant Prostate Cancer

On August 11, 2023, the US Food and Drug Administration (FDA) granted approval to niraparib and abiraterone acetate plus prednisone for patients with deleterious or suspected deleterious BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC), as detected by an FDA approved test.

This approval was based on efficacy findings from cohort 1 of the randomized, double-blind, placebo-controlled MAGNITUDE trial. In this cohort, researchers enrolled 423 patients with homologous recombination repair (HRR) gene-mutated mCRPC who had not previously undergone prior systemic therapy in the mCRPC setting, except for a short course of prior abiraterone acetate plus prednisone and ongoing androgen deprivation therapy (ADT). Patients were allowed to have previously received prior treatment with docetaxel or androgen-receptor (AR) targeted therapies in earlier disease settings. Researchers required patients to have previously undergone an orchiectomy, if not they were required to receive gonadotropin-releasing hormone (GnRH) analogues for the duration of treatment. Among all patients, 225 harbored a prospectively determined BRCA gene mutation (BRCAm) and 198 harbored non-BRCA HRR mutations.

Patients were randomized on a 1:1 basis to receive either niraparib (200 mg) and abiraterone acetate (1000 mg) plus prednisone (10 mg), or placebo and abiraterone acetate plus prednisone daily until disease progression or unacceptable toxicity. Randomization was stratified based on prior administration of either docetaxel, AR targeted therapy, or abiraterone acetate plus prednisone, and BRCA status. The major efficacy outcome measure was radiographic progression-free survival (rPFS), assessed by blinded independent central review, based on RECIST version 1.1 for soft tissue and Prostate Cancer Working Group 3 criteria for bone. Researchers additionally sought an exploratory end point of overall survival (OS). 

At rPFS analysis, patients with BRCAm disease achieved an rPFS of 16.6 months in the niraparib arm compared to that of 10.9 months in the placebo arm (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.36 to 0.79; P = .0014). At the time of OS analysis, median OS was 30.4 months in the niraparib arm and 28.6 months in the placebo arm. Despite observing a statistically significant improvement in rPFS in the overall intention to treat (ITT) HRR population (HR, 0.73; 95% CI, 0.56 to 0.96; P = .0217), patients with non-BRCA HRR mutations displayed an rPFS HR of 0.99 and an OS HR of 1.13, signifying that overall results were primarily attributed to results from the subgroup of patients with BRCAm disease.

The most common adverse reactions occurring in ≥20% patients included decreased hemoglobin, lymphocytes and white blood cells, musculoskeletal pain, fatigue, decreased platelets, increased alkaline phosphatase, constipation, hypertension, nausea, decreased neutrophils, increased creatinine, increased potassium, decreased potassium, and increased aspartate aminotransferase (AST). Among all patients treated in this cohort, 27% required a blood transfusion, including 11% who required multiple transfusions.

Source: 

FDA approves niraparib and abiraterone acetate plus prednisone for BRCA-mutated metastatic castration-resistant prostate cancer. US Food and Drug Administration. August 11, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-and-abiraterone-acetate-plus-prednisone-brca-mutated-metastatic-castration?utm_medium=email&utm_source=govdelivery