Prostate-specific antigen analyses in propel: abiraterone and olaparib versus abiraterone and placebo as first-line therapy for metastatic castration-resistant prostate cancer

You have accessJournal of UrologyCME1 Apr 2023MP11-16 PROSTATE-SPECIFIC ANTIGEN ANALYSES IN PROPEL: ABIRATERONE AND OLAPARIB VERSUS ABIRATERONE AND PLACEBO AS FIRST-LINE THERAPY FOR METASTATIC CASTRATION-RESISTANT PROSTATE CANCER Fred Saad, Andrew J. Armstrong, Antoine Thiery-Vuillemin, Mototsugu Oya, Neal Shore, Giuseppe Procopio, Joao Daniel Guedes, Cagatay Arslan, Niven Mehra, Francis Parnis, Kurralta Park, Australia, Emma Brown, Friederike Schlürmann, Jae Young Joung, Mikio Sugimoto, A. Oliver Sartor, Christian Poehlein, Elizabeth A. Harrington, Laura Barker, Paula Michelle del Rosario, and Noel Clarke Fred SaadFred Saad More articles by this author , Andrew J. ArmstrongAndrew J. Armstrong More articles by this author , Antoine Thiery-VuilleminAntoine Thiery-Vuillemin More articles by this author , Mototsugu OyaMototsugu Oya More articles by this author , Neal ShoreNeal Shore More articles by this author , Giuseppe ProcopioGiuseppe Procopio More articles by this author , Joao Daniel GuedesJoao Daniel Guedes More articles by this author , Cagatay ArslanCagatay Arslan More articles by this author , Niven MehraNiven Mehra More articles by this author , Francis ParnisFrancis Parnis More articles by this author , Kurralta ParkKurralta Park More articles by this author , Australia Australia More articles by this author , Emma BrownEmma Brown More articles by this author , Friederike SchlürmannFriederike Schlürmann More articles by this author , Jae Young JoungJae Young Joung More articles by this author , Mikio SugimotoMikio Sugimoto More articles by this author , A. Oliver SartorA. Oliver Sartor More articles by this author , Christian PoehleinChristian Poehlein More articles by this author , Elizabeth A. HarringtonElizabeth A. Harrington More articles by this author , Laura BarkerLaura Barker More articles by this author , Paula Michelle del RosarioPaula Michelle del Rosario More articles by this author , and Noel ClarkeNoel Clarke More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003226.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract 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 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e131 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fred Saad More articles by this author Andrew J. Armstrong More articles by this author Antoine Thiery-Vuillemin More articles by this author Mototsugu Oya More articles by this author Neal Shore More articles by this author Giuseppe Procopio More articles by this author Joao Daniel Guedes More articles by this author Cagatay Arslan More articles by this author Niven Mehra More articles by this author Francis Parnis More articles by this author Kurralta Park More articles by this author Australia More articles by this author Emma Brown More articles by this author Friederike Schlürmann More articles by this author Jae Young Joung More articles by this author Mikio Sugimoto More articles by this author A. Oliver Sartor More articles by this author Christian Poehlein More articles by this author Elizabeth A. Harrington More articles by this author Laura Barker More articles by this author Paula Michelle del Rosario More articles by this author Noel Clarke More articles by this author Expand All Advertisement PDF downloadLoading ...