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 mCRPC.

The safety profile of the combination therapy was manageable despite its elevated toxicity

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 mCRPC2. 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