The PROpel trial assessed the combination of olaparib + abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms. Kaplan-Meier PFS curves were digitally reconstructed and differences in restricted mean survival time (ΔRMST) were computed. Combination therapy yielded longer PFS (24-mo ΔRMST 1.5 mo, 95% confidence interval 0.6-2.4) in comparison to novel hormonal treatments alone. However, the lack of mature overall survival data, higher complication rates, and higher health care costs are limitations of combination therapy. Ultimately, combining treatments, rather than molecularly targeted sequencing in cases of failure, might not be justified in unselected patients with mCRPC.
A recent trial showed that for metastatic prostate cancer that does not respond to hormone treatment, combined therapy with two drugs (olaparib and abiraterone) may prolong survival free from cancer progression. We included these data in an analysis of three trials that confirmed a small benefit. This combination approach has higher complication rates and is more expensive, and longer-term results for overall survival are needed.
European urology open science. 2023 Apr 29*** epublish ***
Giuseppe Fallara, Daniele Robesti, Daniele Raggi, Francesco Montorsi, Andrea Necchi, Matthew R Cooperberg, Bernard Malavaud, Guillaume Ploussard, Alberto Martini
Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Medical Oncology, Ospedale San Raffaele, Milan, Italy., Departments of Urology and Epidemiology & Biostatistics, University of California-San Francisco, San Francisco, CA, USA., Department of Urology, Institut Universitaire du Cancer Toulouse-Oncopôle, Toulouse, France., Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France.