Lynparib/olaparib combined with abiraterone improves imaging PFS and OS in BRCA+mCRPC

Based on PROpel published in2025 Post hoc analysis of the phase 3 trial (NCT03732820) adding olaparib to abiraterone acetate compared with placebo plus abiraterone , demonstrated clinical benefit in terms of radiographic progression-free survival (rFS) and overall survival (OS) as a first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) and germline or somatic BRCA mutations.

About the germlinerPFS (n=25) in patients with BRCA mutations,event rates were 33.3% and 100% in the olaparib/abiraterone (n=15) and placebo/abiraterone (n=10) groups, respectively. ; Compared with 6.9 months, median rPFS (NR) was not reached (HR, 0.13; 95% CI, 0.04-0.38). Among patients with somatic BRCA mutations (n=52), event rates were 25.9% in the olaparib/abiraterone group (n=27) and 68.0% in the placebo/abiraterone group (n=25); median rPFS was NR vs 11.1 months (HR, 0.19; 95% CI, 0.07-0.45).

In addition, the OS event rates in patients with germline BRCA mutations were 33.3% and 90.0% in the olaparib/abiraterone and placebo/abiraterone groups, respectively; the median OS was NR vs 18.4 months (HR, 0.23; 95% CI, 0.07-0.67). Among patients with somatic BRCA mutations, the OS event rates were 22.2% in the olaparib/abiraterone group and 60.0% in the placebo/abiraterone group; median OS was NR vs 27.5 months (HR, 0.26; 95% CI, 0.09-0.65).

First-line use of olaparib plus abiraterone has clinical benefit on rPFS and OS in patients withmCRPC and germline or somatic BRCA mutations. Therefore, the findings highlight the importance of comprehensive biomarker testing, including tumor tissue and circulating tumor DNA [ctDNA] testing, to inform treatment options, such as intensifying treatment with olaparib plus abiraterone.

In May 2023, the U.S. Food and Drug Administration (FDA) approved olaparib/abiraterone for the treatment of patients with harmful or suspected harmful BRCA-mutated mCRPC, as determined by an FDA-approved companion diagnostic test. inAt the cutoff of the primary analysis in July 2021, the trial met its primary endpoint of rPFS, showing that rPFS was significantly longer with olaparib/abiraterone versus placebo/abiraterone, with a HR of 0.66; 95% CI, 0.54-0.81; P<0.001).

The multicenter, randomized, double-blind, placebo-controlledPROpel study evaluated the efficacy, safety and tolerability of first-line olaparib/abiraterone versus placebo/abiraterone in patients with mCRPC who had not previously received chemotherapy or a new hormonal agent (NHA) for mCRPC. In addition to investigator-assessed rPFS and OS, which are the primary and key secondary endpoints, respectively, other planned analyzes include time to first subsequent treatment or death; prostate-specific antigen (PSA) progression; time to second progression or death; PSA decline of 50% or more from baseline; health-related quality of life; objective response rate; homologous recombination repair (HRR) mutation status; and safety and tolerability.

At the October 2022 data cutoff, the median of patients in the olapar/abiraterone and placebo/abiraterone groups in the ITT population was /span>OS was 42.1 months and 34.7 months respectively, with bilateral borderline significance of 0.0377 (HR, 0.81; 95% CI, 0.67-1.00; P=0.0544). The median OS of patients in the BRCA mutation subgroup was NR, and the median OS of patients in the olapar/abiraterone and placebo/abiraterone groups was 23.0 months (HR, 0.29; 95% CI, 0.14-0.56).

Reference materials:https://www.onclive.com/view/olaparib-plus-abiraterone-improves-radiographic-pfs-and-os-in-brca-mcrpc