Introduction and objective
PROpel met its primary endpoint of a significant radiographic progression-free survival (rPFS) benefit with abiraterone (abi) and olaparib (ola) vs abi and placebo (pbo) in the 1L treatment of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) enrolled irrespective of homologous recombination repair gene mutation (HRRm) status (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P<0.001). Exploratory analyses of rPFS favored abi and ola vs abi and pbo for pts with and without HRRm and/or a BRCA mutation (BRCAm). A trend towards overall survival benefit with abi and ola was observed. PSA is known to be regulated by the androgen receptor. We report post hoc exploratory analyses of prostate-specific antigen (PSA) response and time to PSA progression at a 2nd data cut-off (14/03/22) for pts with and without HRR and/or BRCA mutations.
Methods
PROpel was a phase 3 double-blind trial. Pts were randomized 1:1 to receive ola (300 mg twice daily [bid]) or pbo, and abi (1000 mg once daily) + prednisone/prednisolone (5 mg bid) until disease progression, unacceptable toxicity or withdrawal of consent. PSA response rate was the % of pts with a ≥50% decrease in PSA from baseline to lowest post-baseline result, confirmed by a 2nd consecutive PSA result ≥3 weeks later. Time to PSA progression was time from randomization to 1st PSA progression per Prostate Cancer Working Group 3 criteria. Aggregated results from tumor tissue (FoundationOne®CDx) and circulating tumor DNA (FoundationOne®Liquid CDx) tests were used to classify HRRm and BRCAm status.
Results
Confirmed PSA response rate was 79.3% with abi and ola vs 69.2% with abi and pbo in the overall population, and ≥7% higher with abi and ola vs abi and pbo in each subgroup. Time to PSA progression was prolonged with abi and ola vs abi and pbo in the overall and subgroup populations (BRCAm HR 0.14; 95% CI 0.07–0.25; HRRm HR 0.41; 95% CI 0.29–0.59; Table 1).
Conclusions
In this exploratory analysis, 1L mCRPC treatment with abi and ola resulted in higher PSA response rates and prolonged time to PSA progression vs abi and pbo in all pts, with more pronounced improvements in the HRRm and BRCAm subgroups. These results are consistent with the primary rPFS benefit previously reported.
Source of funding
AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who are codeveloping olaparib