In PROpel (NCT03732820), olaparib + abiraterone resulted in a statistically significant radiographic progression-free survival (rPFS) benefit and numerically prolonged overall survival (OS) versus placebo + abiraterone in first-line (1L) metastatic castration-resistant prostate cancer (mCRPC) patients. Here, we report post hoc exploratory subgroup analyses in patients with asymptomatic/mildly symptomatic or symptomatic disease at baseline.
Patients were randomised 1:1 to olaparib (300 mg b.i.d.) or placebo with abiraterone (1000 mg o.d.) + prednisone/prednisolone (5 mg b.i.d.). For this post hoc exploratory analysis, patients with a Brief Pain Inventory-Short Form (BPI-SF) item 3 score of <4 and no opiate use were classified as asymptomatic/mildly symptomatic; those with a BPI-SF item 3 score of ≥4 and/or opiate use were classified as symptomatic. Subgroup analyses included investigator-assessed rPFS, OS, objective response rate, time to second progression or death, health-related quality of life, and safety.
The median rPFS in asymptomatic/mildly symptomatic patients (n = 560) was 27.6 mo for olaparib + abiraterone versus 19.1 mo for placebo + abiraterone (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.46-0.76). For symptomatic patients (n = 183), equivalent values were 14.1 versus 13.8 mo (HR, 0.78; 95% CI, 0.54-1.13). At the final planned OS analysis, the median OS in asymptomatic/mildly symptomatic patients was not reached for olaparib + abiraterone versus 39.5 mo for placebo + abiraterone (HR, 0.77; 95% CI, 0.59-1.00). For symptomatic patients, equivalent values were 22.9 versus 22.8 mo (HR, 0.82; 95% CI, 0.58-1.16). Other outcomes showed no meaningful differences between the subgroups.
Olaparib + abiraterone provided efficacy benefits in 1L mCRPC patients with either asymptomatic/mildly symptomatic or symptomatic disease. A larger benefit occurred in asymptomatic/mildly symptomatic patients.
PROpel, a phase 3 clinical trial, looked at whether combining olaparib with abiraterone delays the progression of patients' cancer compared with placebo plus abiraterone. Patients with or without pain symptoms associated with metastatic castration-resistant prostate cancer were eligible for enrolment into the trial. Results showed that olaparib plus abiraterone reduced the risk of disease progression and death, with a larger benefit observed in patients without or with mild pain symptoms than in those with pain symptoms.
European urology oncology. 2024 Oct 08 [Epub ahead of print]
Noel W Clarke, Andrew J Armstrong, Mototsugu Oya, Neal Shore, Giuseppe Procopio, João Daniel Guedes, Cagatay Arslan, Niven Mehra, Francis Parnis, Emma Brown, Friederike Schlürmann, Jae Young Joung, Mikio Sugimoto, Oliver Sartor, Christian Poehlein, David McGuinness, Arnold Degboe, Fred Saad
The Christie and Salford Royal NHS Foundation Trusts, Manchester, UK. Electronic address: ., Duke Cancer Institute Center for Prostate and Urologic Cancer, Duke University, Durham, NC, USA., Keio University School of Medicine, Tokyo, Japan., Carolina Urologic Research Center, Myrtle Beach, SC, USA., Programma Prostata Oncologia Medica Genitourinaria Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy., Hospital de Base de São José do Rio Preto, São José do Rio Preto, Brazil., Izmir Economy University Medical Park Hospital, Karsiyaka, Turkey., Raboud University Medical Center, Nijmegen, The Netherlands., Ashford Cancer Centre Research, Kurralta Park, SA, Australia., University Hospital Southampton, Southampton, UK., Centre Hospitalier de Cornouaille, Quimper, France., National Cancer Center, Goyang-si, South Korea., Kagawa University Hospital, Kagawa, Japan., Tulane Cancer Center, New Orleans, LA, USA., Merck & Co. Inc, Rahway, NJ, USA., Global Medicines Development, Oncology R&D, AstraZeneca, Cambridge, UK., Global Medicines Development, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA., Centre Hospitalier de l'Université de Montréal/Centre de recherche du Centre Hospitalier de l'Université de Montréal, Université de Montreal, Montreal, QC, Canada.