Previously, the PROpel study demonstrated a statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in the first-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). This analysis presents data from the key secondary endpoint of overall survival, which, although not significantly different between arms, provides further insight into the clinical benefit of olaparib plus abiraterone as a first-line mCRPC treatment.
In real-world clinical practice, the median overall survival (OS) of patients with metastatic castration-resistant prostate cancer (mCRPC) is less than two years. PROpel was the first phase III trial of a PARP inhibitor in combination with a next-generation hormonal agent showing a statistically significant and clinically meaningful improvement in radiographic progression-free survival (PFS) with olaparib plus abiraterone versus placebo plus abiraterone in a homologous recombination repair mutation (HRRm)-unselected first-line mCRPC population. This analysis presents data from the key secondary endpoint of overall survival (OS).
The purpose of this study was to evaluate the efficacy and safety of the combination of olaparib and abiraterone versus placebo and abiraterone in patients with mCRPC who have received no prior cytotoxic chemotherapy or new hormonal agents at mCRPC stage.1
METHODS
PROpel was a randomised, double-blind, phase III trial conducted at 126 centres in seventeen countries worldwide. Patients with mCRPC aged at least eighteen years, with an ECOG PS 0-1 and a life expectancy of at least six months who did not receive previous systemic treatment for mCRPC were randomly assigned (1:1) to receive abiraterone acetate (orally, 1000 mg once daily) plus prednisone or prednisolone with either olaparib (orally, 300 mg twice daily) or placebo. Importantly, patients in this trial were unselected for HRRm status. Radiographic progression-free survival (PFS) was the primary endpoint, with overall survival (OS) as a key secondary endpoint.
FINDINGS
Between 31 October 2018 and 11 March 2020, 1,103 patients were screened, of whom 399 were randomly assigned to olaparib plus abiraterone and 397 to placebo plus abiraterone. After a median follow-up for OS of 36 months, the median OS was reported at 42.1 months for olaparib plus abiraterone as compared to 34.7 months with placebo plus abiraterone (HR[95%CI]: 0.81[0.67-1.00]; p=0.054). Anaemia was the most common grade 3–4 adverse event, reported in 64 (16%) of the 398 patients in the olaparib plus abiraterone cohort and 13 (3%) of the 396 patients in the placebo plus abiraterone cohort. Serious adverse events were reported in 161 (40%) patients in the olaparib plus abiraterone cohort and 126 (32%) patients in the placebo plus abiraterone cohort. One death in the placebo plus abiraterone cohort (from interstitial lung disease) was considered treatment-related.
CONCLUSION
Overall survival was not significantly different between treatment groups at the final pre-specified analysis.2 However, it is worth noting that the primary endpoint of radiographic PFS was successfully achieved, demonstrating a statistically significant and clinically significant advantage for the olaparib plus abiraterone group. Further research will help to understand the potential clinical benefit of olaparib plus abirateronein patients with mCRPC with and without HRR mutations.
REFERENCES
1. ClinicalTrials.gov ID NCT03732820. A Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (PROpel Study). https://clinicaltrials.gov/study/NCT03732820?term=NCT03732820&rank=1. Accessed on 5 October 2023.
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