The PROpel study (NCT03732820) demonstrated a statistically significant progression-free survival benefit with olaparib plus abiraterone versus placebo plus abiraterone in the first-line metastatic castration-resistant prostate cancer (mCRPC) setting, irrespective of homologous recombination repair mutation status.
We report additional safety analyses from PROpel to increase clinical understanding of the adverse-event (AE) profiles of olaparib plus abiraterone versus placebo plus abiraterone.
A randomised (1:1), double-blind, placebo-controlled trial was conducted at 126 centres in 17 countries (October 2018-January 2020). Patients had mCRPC and no prior systemic mCRPC treatment.
Olaparib (300 mg bid) or placebo with abiraterone (1000 mg od) plus prednisone/prednisolone (5 mg bid).
The data cut-off date was July 30, 2021. Safety was assessed by AE reporting (Common Terminology Criteria for Adverse Events v4.03) and analysed descriptively.
The most common AEs (all grades) for olaparib plus abiraterone versus placebo plus abiraterone were anaemia (46.0% vs 16.4%), nausea (28.1% vs 12.6%), and fatigue (27.9% vs 18.9%). Grade ≥3 anaemia occurred in 15.1% versus 3.3% of patients in the olaparib plus abiraterone versus placebo plus abiraterone arm. The incidences of the most common AEs for olaparib plus abiraterone peaked early, within 2 mo, and were managed typically by dose modifications or standard medical practice. Overall, 13.8% versus 7.8% of patients discontinued treatment with olaparib plus abiraterone versus placebo plus abiraterone because of an AE; 3.8% versus 0.8% of patients discontinued because of anaemia. More venous thromboembolism events were observed in the olaparib plus abiraterone arm (any grade, 7.3%; grade ≥3, 6.8%) than in the placebo plus abiraterone arm (any grade, 3.3%; grade ≥3, 2.0%), most commonly pulmonary embolism (6.5% vs 1.8% for olaparib plus abiraterone vs placebo plus abiraterone).
Olaparib plus abiraterone has a manageable and predictable safety profile.
The PROpel trial showed that in patients who had not received any previous treatment for metastatic castration-resistant prostate cancer, olaparib combined with abiraterone was more effective in delaying progression of the disease than abiraterone alone. Most side effects caused by combining olaparib with abiraterone could be managed with supportive care methods, by pausing olaparib administration for a short period of time and/or by reducing the dose of olaparib.
European urology oncology. 2024 Apr 05 [Epub ahead of print]
Fred Saad, Andrew J Armstrong, Mototsugu Oya, Karina Vianna, Mustafa Özgüroğlu, Craig Gedye, Gary L Buchschacher, Ji Youl Lee, Urban Emmenegger, Jiri Navratil, Juan Antonio Virizuela, Anibal Salazar, Denis Maillet, Hiroji Uemura, Jeri Kim, Emma Oscroft, Laura Barker, Arnold Degboe, Noel W Clarke
Centre Hospitalier de l'Université de Montréal/CRCHUM, Université de Montréal, Montreal, QC, Canada. Electronic address: ., Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC, USA., Keio University School of Medicine, Tokyo, Japan., Centro Integrado de Oncologia de Curitiba, Curitiba, Brazil., Istanbul University Cerrahpaşa, Faculty of Medicine, Istanbul, Türkiye., Calvary Mater Newcastle, Waratah, NSW, Australia., Kaiser Permanente Southern California, Los Angeles, CA, USA., The Catholic University of Korea Seoul St Mary's Hospital, Seoul, South Korea., Sunnybrook Research Institute, Toronto, ON, Canada., Masaryk Memorial Cancer Institute, Brno, Czech Republic., Hospital Universitario Virgen Macarena, Sevilla, Spain., Instituto de Especialidades Urologicas, Santiago, Chile., Centre Hospitalier Lyon Sud, Pierre-Bénite, France; Faculté de Médecine Jacques Lisfranc, Saint-Etienne, France., Yokohama City University Medical Center, Kanagawa, Japan., Merck & Co., Inc., Rahway, NJ, USA., AstraZeneca, Cambridge, UK., AstraZeneca, Baltimore, MD, USA., The Christie and Salford Royal Hospital NHS Foundation Trusts, and University of Manchester, Manchester, UK.