Adding olaparib to first-line treatment with abiraterone extends overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to the final analysis of the phase 3 PROpel trial.1
Patients who received the combination had a median OS of 42 months, which is the longest median OS reported to date for a phase 3 trial in the first-line mCRPC setting, said Noel W. Clarke, MBBS, of the Christie and Salford Royal NHS Foundation Trusts in Manchester, UK. Dr Clarke presented these results at the 2023 ASCO Genitourinary Cancers Symposium.
The PROpel trial (ClinicalTrials.gov Identifier: NCT03732820) enrolled 796 patients with mCRPC. Patients were randomly assigned to receive olaparib plus abiraterone (399 patients) or placebo plus abiraterone (397 patients).
Baseline characteristics were well balanced between the arms. The median age was 69 (range, 43-91) years in the olaparib-abiraterone arm and 70 (range, 46-88) years in the abiraterone-alone arm. Nearly 30% of patients in each arm had HRR mutations.
In a prior analysis, there was a significant improvement in radiographic progression-free survival (rPFS) with olaparib plus abiraterone.2 The investigator-assessed median rPFS was 24.8 months in the combination arm and 16.6 months in the monotherapy arm (HR, 0.66; 95% CI, 0.54-0.81; P <.001).
In this final analysis, the median OS was 42.1 months in the combination arm and 34.7 months in the monotherapy arm (hazard ratio [HR], 0.81; 95% CI, 0.67-1.00; P =.0544; 47.9% maturity).1 There was a trend toward an OS benefit with olaparib across subgroups.
The median time to first subsequent therapy was 24.6 months in the combination arm and 19.4 months in the monotherapy arm (HR, 0.76; 95% CI, 0.64-0.90). The median second progression-free survival was not reached in either arm (HR, 0.76; 95% CI, 0.59-0.99).
No new long-term safety issues were observed, Dr Clarke said. The rate of grade 3 or higher adverse events (AEs) was 55.8% in the combination arm and 43.2% in the monotherapy arm. The most common grade 3 or higher AE was anemia (16.1%) in the combination arm and hypertension in the monotherapy arm (4.5%). The rate of fatal AEs was 6.5% and 5.1%, respectively.
“The overall results, in conclusion, support combination treatment with abiraterone and olaparib as an important new first-line treatment in patients with mCRPC,” Dr Clarke said.
Disclosures: This research was supported by AstraZeneca in collaboration with Merck Sharp & Dohme Corp. None of the study authors have relevant disclosures.
1. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Final overall survival (OS) in PROpel: Abiraterone (abi) and olaparib (ola) versus abiraterone and placebo (pbo) as first-line (1L) therapy for metastatic castration-resistant prostate cancer (mCRPC). ASCO GU 2023. February 16-18, 2023. Abstract LBA16.
2. Clarke NW, Armstrong AJ, Thiery-Vuillemin A, et al. Abiraterone and olaparib for metastatic castration-resistant prostate cancer. Published online June 3, 2022. NEJM Evid. https://doi.org/10.1056/EVIDoa2200043