Olaparib Plus Abiraterone in Asian Patients With Metastatic Castration-Resistant Prostate Cancer: PROpel Subset Analysis

Abstract

In the phase 3 PROpel trial (NCT03732820) patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib plus abiraterone in the first-line setting showed significantly prolonged radiographic progression-free survival (rPFS; primary data cutoff [DCO]: 30 July 2021; hazard ratio [HR] 0.66, 95% confidence interval [CI], 0.54-0.81; p < 0.001), and at prespecified final OS analysis DCO (12 October 2022) numerically prolonged overall survival (OS; HR 0.81, 95% CI, 0.67-1.00; p = 0.054), versus placebo plus abiraterone for the global population. Here, we report efficacy, safety, and patient-reported outcome data for the Asian subset in PROpel. Eligible patients were randomly assigned (1:1) to either olaparib (300 mg twice daily) or placebo in combination with abiraterone (1000 mg once daily). The primary endpoint was investigator-assessed rPFS, and a key secondary endpoint was OS. In the Asian subset (n = 133) at primary analysis, median rPFS was 27.6 months in the olaparib plus abiraterone arm (n = 63), compared with 19.3 months in the placebo plus abiraterone arm (n = 70; HR 0.55, 95% CI, 0.32-0.95). Median OS at the final analysis was not reached in the olaparib plus abiraterone arm versus 43.7 months in the placebo plus abiraterone arm (HR 0.59, 95% CI, 0.32-1.06). The safety profile was generally similar in the Asian subset and the global population. Efficacy and safety results for olaparib plus abiraterone in the Asian subset were generally consistent with the global PROpel population supporting the combination of olaparib plus abiraterone as an important first-line treatment for consideration in Asian patients with mCRPC. Trial Registration: Clinicaltrials.gov identifier: NCT03732820.

Keywords: Asian; abiraterone; metastatic castration‐resistant prostate cancer; olaparib; progression‐free survival.

FIGURE 1

Kaplan–Meier estimate curves for rPFS by investigator assessment in the Asian subset (DCO: 30 July 2021). A circle indicates a censored observation. HR and CIs were calculated using a Cox proportional hazards model adjusted for the variables selected in the primary pooling strategy: metastases and docetaxel treatment at mHSPC stage. CI, confidence interval; DCO, data cutoff; HR, hazard ratio; mHSPC, metastatic hormone‐sensitive prostate cancer; NC, not calculable; rPFS, radiographic progression‐free survival.

FIGURE 2

Kaplan–Meier estimate curves for OS in the Asian subset (DCO: 12 October 2022). A circle indicates a censored observation. HR and CIs were calculated using a Cox proportional hazards model adjusted for the variables selected in the primary pooling strategy: metastases and docetaxel treatment at mHSPC stage. CI, confidence interval; DCO, data cutoff; HR, hazard ratio; NC, not calculable; mHSPC, metastatic hormone‐sensitive prostate cancer; OS, overall survival.

FIGURE 3

Kaplan–Meier estimate curves for TFST in the Asian subset (DCO: 12 October 2022). A circle indicates a censored observation. HR and CIs were calculated using a Cox proportional hazards model adjusted for the variables selected in the primary pooling strategy: metastases and docetaxel treatment at mHSPC stage. CI, confidence interval; DCO, data cutoff; HR, hazard ratio; mHSPC, metastatic hormone‐sensitive prostate cancer; NC, not calculable; TFST, time to first subsequent therapy.