Recent oncology guidelines recommend BRCA1/2 testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive metastatic castration-resistant PCa (mCRPC) patients following prior treatment with abiraterone, enzalutamide or docetaxel. However, the question of which of these standard treatments is the most effective for BRCA1/2 positive mCRPC patients remains to be answered. The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA1/2 mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free survival (PFS) and overall survival (OS).
As no interventional trials are available on this topic, we performed the data synthesis of BRCA1/2 positive mCRPC patients by using both proportional and individual patient data. For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used individual patient data with random effect Cox regression calculations.
Our meta-analysis included 16 eligible studies with 348 BRCA1/2 positive mCRPC patients. In the first treatment line, response rates for abiraterone, enzalutamide and docetaxel were 52% (CI: 25-79%), 64% (CI: 43-80%) and 55% (CI: 36-73%), respectively. Analyses of individual patient data revealed a PFS (HR: 0.47, CI: 0.26-0.83, p = 0.010) but no OS (HR: 1.41, CI: 0.82-2.42, p = 0.210) benefit for enzalutamide compared to abiraterone-treated patients.
Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2 positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCA positive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.
Prostate cancer and prostatic diseases. 2022 Dec 12 [Epub ahead of print]
Tamás Fazekas, Ádám D Széles, Brigitta Teutsch, Anita Csizmarik, Bálint Vékony, Alex Váradi, Tamás Kói, Zsolt Lang, Nándor Ács, Zsolt Kopa, Péter Hegyi, Boris Hadaschik, Viktor Grünwald, Péter Nyirády, Tibor Szarvas
Department of Urology, Semmelweis University, Budapest, Hungary., Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany., Department of Urology, Semmelweis University, Budapest, Hungary. .