PROpel: Good results for abiraterone plus olaparib in mCRPC

Exploratory endpoints of the phase 3 PROpel trial favoured first-line abiraterone plus olaparib over abiraterone plus placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The safety profile of the combination regimen was manageable and consistent with the known safety profiles of the individual agents [1].

The primary analysis of the global, randomised, double-blind, phase 3 PROpel trial (NCT03732820; n=797) demonstrated a significant benefit of first-line abiraterone plus olaparib over abiraterone plus placebo in terms of radiographic progression or death (rPFS) in patients with mCRPC [2]. Prof. Noel Clarke (University of Manchester, UK) presented exploratory endpoints of this trial during a game-changing session.

First, Prof. Clarke emphasised that the effect of the combination regimen on rPFS was consistent in patients with homologous recombination repair gene mutations (HRRm; HR 0.50; 95% CI 0.34–0.73) and patients without mutations (HR 0.76; 95% CI 0.60–0.97). Second, a positive trend could be observed in the overall survival data in favour of the combination regimen (HR 0.86; P=0.29), but the results were only 28.6% mature at the time of the analysis. Other secondary endpoints displayed a significant benefit for patients who received abiraterone and olaparib, such as ‘time to first subsequent therapy or death’ (HR 0.74; P=0.004) and ‘time to second progression or death’ (PFS2; HR 0.69; P=0.0184). Similarly, in patients with measurable disease (n=321), the overall response rate was higher in patients receiving the combination therapy (58.4% vs 48.1%; P=0.0409). PSA response rates showed a clinical benefit of the combination regimen as well (HR 0.55; 95% CI 0.45–0.68).

Prof. Clarke added that the toxicity of abiraterone plus olaparib was elevated compared with abiraterone alone, but that the safety profile of the combination therapy was nevertheless manageable. Anaemia (46.0%), fatigue (37.2%), and nausea (28.1%) were the most prevalent any-grade adverse events in the experimental group.

1. Clarke N, et al. Exploratory endpoints from PROpel: A Phase III trial of abiraterone + olaparib vs. abiraterone + placebo in 1st line metastatic castration-resistant prostate cancer. Game-changing session 5, EAU 2022, 01–04 July.
2. Clarke N, et al. NEJM Evidence. 2022;EVIDoa2200043

 

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Posted on 22 July 202217 May 2024