Olaparib plus Abiraterone for Metastatic Castration-resistant Prostate Cancer: Pharmacokinetics Data from the PROpel Trial

Abstract

PROpel (NCT03732820) was a positive phase 3 trial that demonstrated a clinically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in first-line metastatic castration-resistant prostate cancer. For a subset of PROpel patients, steady-state concentrations of olaparib, abiraterone, and Δ⁴-abiraterone were measured in blood samples collected before and at several time points after dose administration. The pharmacokinetics (PK) for each drug and metabolite were evaluated to determine whether any clinically relevant drug-drug interactions between olaparib and abiraterone occurred. The results demonstrate that steady-state PK parameters for olaparib and abiraterone in PROpel were comparable with those in monotherapy trials. Abiraterone steady-state exposures were similar between treatment arms. Δ⁴-Abiraterone had slightly lower steady-state exposures when abiraterone was administered in combination with olaparib. These results are consistent with a previous phase 2 study, supporting the conclusion that no clinically relevant PK-based drug-drug interactions occurred when olaparib and abiraterone were given in combination at their full monotherapy doses. PATIENT SUMMARY: When drugs are administered in combination, a key consideration is whether there are any interactions between the drugs that may affect their activity. We analyzed blood concentrations of olaparib and abiraterone in a subset of patients with prostate cancer from the PROpel trial to determine if there were interactions between these two drugs. We found that there was no significant effect on the profile of either drug when they were given together at the same doses used when each drug is given individually.

Keywords: Abiraterone; Metastatic castration-resistant prostate cancer; Olaparib; Pharmacokinetics.