METHODS: We conducted a double-blind, phase 3 trial of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status. HRRm status was determined following enrollment by tumor tissue and circulating tumor DNA tests. Patients were randomly assigned (1:1) to receive abiraterone (1000 mg once daily) plus prednisone or prednisolone with either olaparib (300 mg twice daily) or placebo. The primary end point was imaging-based progression-free survival (ibPFS) by investigator assessment. Overall survival was among the secondary end points.
RESULTS: At this planned primary analysis at the first data cutoff, median ibPFS was significantly longer in the abiraterone and olaparib arm than in the abiraterone and placebo arm (24.8 vs. 16.6 months; hazard ratio, 0.66; 95% confidence interval [CI], 0.54 to 0.81; P<0.001) and was consistent with blinded independent central review (hazard ratio, 0.61; 95% CI, 0.49 to 0.74). At this data cutoff, overall survival data were immature (28.6% maturity; hazard ratio, 0.86; 95% CI, 0.66 to 1.12; P=0.29). The safety profile of olaparib and abiraterone was consistent with the known safety profiles of the individual drugs. The most common adverse events in the abiraterone and olaparib arm were anemia, fatigue/asthenia, and nausea.
CONCLUSIONS: At primary analysis at this first data cutoff, abiraterone combined with olaparib significantly prolonged ibPFS compared with abiraterone and placebo as first-line treatment for patients with mCRPC enrolled irrespective of HRRm status. (Funded by AstraZeneca and Merck Sharp & Dohme, LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; ClinicalTrials.gov number, NCT03732820.)
Noel W. Clarke, M.B.B.S., Ch.M., F.R.C.S.1, Andrew J. Armstrong, Sc.M., M.D.2, Antoine Thiery-Vuillemin, M.D., Ph.D.3, Mototsugu Oya, M.D.4, Neal Shore, M.D.5, Eugenia Loredo, M.D.6, Giuseppe Procopio, M.D.7, Juliana de Menezes, M.D.8, Gustavo Girotto, M.D.9, Cagatay Arslan, M.D.10, Niven Mehra, M.D., Ph.D.11, Francis Parnis, F.R.A.C.P.12, Emma Brown, M.D.13, Friederike Schlürmann, M.D.14, Jae Y. Joung, M.D., Ph.D.15, Mikio Sugimoto, M.D., Ph.D.16, Juan A. Virizuela, M.D., Ph.D.17, Urban Emmenegger, M.D.18, Jiri Navratil, M.D.19, Gary L. Buchschacher, Jr., M.D., Ph.D.20, Christian Poehlein, M.D.21, Elizabeth A. Harrington, Ph.D.22, Chintu Desai, Ph.D.23, Jinyu Kang, M.D.24, and Fred Saad, M.D., F.R.C.S.25for the PROpel Investigators*
- The Christie and Salford Royal Hospital NHS Foundation Trusts, University of Manchester, Manchester, United Kingdom
- Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC
- Centre Hospitalier Régional Universitaire Hôpital Jean-Minjoz, Besançon, France
- Keio University School of Medicine, Tokyo
- Carolina Urologic Research Center, Myrtle Beach, SC
- Centro de Investigaciones Clinicas Viña del Mar, Valparaíso, Chile
- Fondazione Istituto Nazionale Tumori Milano, Milan
- Hospital Nossa Senhora da Conceição, Porte Alegre, Brazil
- Hospital de Base São José do Rio Preto, São José do Rio Preto, Brazil
- Izmir Economy University Medical Park Hospital, Karsiyaka, Turkey
- Radboud Universitair Medisch Centrum, Nijmegen, Netherlands
- Ashford Cancer Centre Research, Adelaide, South Australia
- University Hospital Southampton, Southampton, United Kingdom
- Centre Hospitalier Intercommunal de Cornouaille, Quimper, France
- National Cancer Center, Goyang, South Korea
- Kagawa University Hospital, Kagawa, Japan
- Hospital Universitario Virgen Macarena, Seville, Spain
- Sunnybrook Research Institute and Odette Cancer Centre, Toronto
- Masaryk Memorial Cancer Institute, Brno, Czech Republic
- Kaiser Permanente Southern California, Los Angeles
- Merck & Co., Inc., Rahway, NJ
- Translational Medicine, Oncology R&D, AstraZeneca, Cambridge, United Kingdom
- Global Medicines Development, Oncology R&D, AstraZeneca, Cambridge, United Kingdom
- Global Medicines Development, Oncology R&D, AstraZeneca, Gaithersburg, MD
- Centre Hospitalier de l’Universite de Montreal, Montreal
Source: Clarke NW, Armstrong AJ, Thiery-Vuillemin A et al. "Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer." NEJM Evidence. 2022. DOI:https://doi.org/10.1056/EVIDoa2200043.