GU Cancers 2022 | PROpel: olaparib plus abiraterone as 1L treatment for metastatic CRPC
Fred Saad, FRCS, MD, Centre Hospitalier de l’Université de Montréal, Montreal, Canada outlines the results of the randomized, double-blind Phase III PROpel (NCT03732820) clinical trial investigating olaparib plus abiraterone as first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) who had not yet been treated. The current standard of care (SOC) for this patient population is chemotherapy with docetaxel, followed by olaparib monotherapy, however, patients tend to progress following treatment, contributing to a poor 5-year overall survival (OS) rate. A total of 796 patients were randomized 1:1 to receive either olaprib plus abiraterone or olaparib monotherapy. The primary endpoint of the Phase III study was radiographic progression-free survival (rPFS) with a key secondary endpoint of OS. The primary endpoint was met at a planned interim-analysis, with patients being treated with olaparib plus abiraterone demonstrating a statistically significant improved rPFS compared to treatment with olaparib alone. Additionally, a trend was observed toward an improved OS at this interim analysis, which will continue to be assessed. The safety profile of each treatment was consistent with what was previously known. This interview took place at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium 2022 in San Francisco, CA
Transcript (edited for clarity)
The PROpel study is a phase III randomized trial taking patients in first-line mCRPC, all comers, no biomarker predetermined eligibility criteria. We allowed patients that have had docetaxel in the pre-mCRPC state, so in metastatic hormone-sensitive, we allowed patients that had even significant pain to come into this study, and we allowed patients with visceral metastases to come into the study...
The PROpel study is a phase III randomized trial taking patients in first-line mCRPC, all comers, no biomarker predetermined eligibility criteria. We allowed patients that have had docetaxel in the pre-mCRPC state, so in metastatic hormone-sensitive, we allowed patients that had even significant pain to come into this study, and we allowed patients with visceral metastases to come into the study. So a real-world mCRPC first-line study in about 800 patients, randomized 1:1 between getting abiraterone and placebo versus abiraterone plus olaparib, and with a primary endpoint of radiographic progression-free survival, and obviously secondary endpoints, very important, overall survival, time to subsequent therapy, time to second progression, adverse events, quality of life, as you would expect for this kind of trial.
The results. Basically, the primary endpoint was largely met, very statistically significant, and in my opinion, very clinically significant improvement in radiographic progression-free survival or death. That was a 34% reduction, which turned out to be over 8 months improvement over abiraterone alone, which is considered one of the most widely used standard of care for first-line mCRPC. Of note, that 8 month improvement is basically identical to what we saw with abiraterone against a pure placebo. And so really, I think we have something that really benefits patients with mCRPC to further improve their outcome with first-line therapy, which unfortunately, is, many times, the only line of therapy patients get in mCRPC.
Overall survival is still immature. We have less than 30% of the deaths that we need for maturity, but we’re already starting to see a trend towards an improved overall survival, and we have other endpoints that encourage us that we’re going in the right direction. Time to subsequent therapy was significantly prolonged in the combination arm and time to second progression was also significantly prolonged in the combination arm. We had better overall response rate in those that had measurable disease. And in terms of adverse events, there was nothing unexpected from either drug used alone, and clearly we did not seem to see an increase in toxicity of either drug when combined together. And overall, quality of life was maintained throughout the study. We never saw any significant difference or deterioration by adding olaparib to abiraterone.
So overall, I think this is a very positive, and probably the first, combination regimen that seems to clearly improve the outcome of patients in first-line mCRPC and we clearly need to be improving on what we’ve been using as standard of care for several years.
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