For patients with metastatic castration-resistant prostate cancer (mCRPC) with homologous recombinant repair (HRR) gene alterations, treatment with niraparib in combination with abiraterone acetate plus prednisone (AAP) as first-line therapy improved radiographic progression-free survival (rPFS) and other clinical outcomes, according to findings presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.
The randomized, placebo-controlled, double-blind, phase 3 MAGNITUDE study (ClinicalTrials.gov Identifier: NCT03748641) assessed the efficacy and safety of niraparib in combination with AAP in patients with mCRPC with or without alterations in HRR associated genes. To be eligible, patients had to have received no more than 4 months of prior AAP treatment.
Of the total study population, 423 patients were positive for HRR gene alterations (HRR BM+). These patients were randomly assigned 1:1 to receive niraparib 200mg orally once daily plus AAP (n=212) or AAP plus placebo (n=211).
The primary endpoint was rPFS, as assessed by blinded independent central review, in the BRCA1/2 group followed by all HRR BM+ patients; rPFS was defined as the time from randomization date to date of radiographic progression or death, whichever occurred first.
After a median follow-up of 18.6 months, results showed that treatment with niraparib plus AAP reduced the risk of progression or death by 47% (16.6 vs 10.9 months, respectively; hazard ratio [HR] 0.53; 95% CI, 0.36-0.79; P =.0014) in the BRCA1/2 subgroup and 27% (16.5 vs 13.7 months, respectively; HR 0.73; 95% CI, 0.56-0.96; P =.0217) in all HRR BM+ patients, compared with the placebo plus AAP.
Additionally, niraparib plus AAP met key secondary endpoints, delaying time to initiation of cytotoxic chemotherapy (HR 0.59; 95% CI, 0.39-0.89; P =.0108), time to symptomatic progression (HR 0.69; 95% CI, 0.47-0.99; P =.0444), and time to prostate-specific antigen (PSA) progression (HR 0.57; 95% CI, 0.43-0.76; P =.0001).
An improvement in objective response rate (relative risk, 2.13; 95% CI, 1.45-3.13; P <.001) was also observed with the combination. As for overall survival, the researchers reported that the first interim analysis of data was immature (HR 0.94; 95% CI, 0.65-1.36; P =.7333).
Among 233 HRR BM- patients, a preplanned futility analysis showed no evidence of benefit with the addition of niraparib to AAP.
As for safety, the incidence of grade 3/4 adverse events and treatment discontinuations in the niraparib plus AAP group was 67% and 9%, respectively, compared with 46.4% and 3.8% in the placebo plus AAP arm.
Findings also showed no clinically significant differences in overall quality of life based on responses on the Functional Assessment of Cancer Therapy-Prostate questionnaire.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Chi KN, Rathkopf DE, Smith MR, et al. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Presented at: 2022 ASCO Genitourinary Cancers Symposium; February 17-19, 2022; San Francisco, CA.
This article originally appeared on MPR