Therapeutic sensitivity to standard treatments in BRCA positive metastatic castration-resistant prostate cancer patients-a systematic review and meta-analysis.

Autor: Fazekas T; Department of Urology, Semmelweis University, Budapest, Hungary.; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Széles ÁD; Department of Urology, Semmelweis University, Budapest, Hungary.; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Teutsch B; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Csizmarik A; Department of Urology, Semmelweis University, Budapest, Hungary., Vékony B; Department of Urology, Semmelweis University, Budapest, Hungary., Váradi A; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Kói T; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.; Department of Stochastics, Institute of Mathematics, Budapest University of Technology and Economics, Budapest, Hungary., Lang Z; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.; Department of Biostatistics, University of Veterinary Medicine Budapest, Budapest, Hungary., Ács N; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.; Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary., Kopa Z; Department of Urology, Semmelweis University, Budapest, Hungary.; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Hegyi P; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary.; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary., Hadaschik B; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany., Grünwald V; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany., Nyirády P; Department of Urology, Semmelweis University, Budapest, Hungary.; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Szarvas T; Department of Urology, Semmelweis University, Budapest, Hungary. szarvas.tibor@med.semmelweis-univ.hu.; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. szarvas.tibor@med.semmelweis-univ.hu.; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany. szarvas.tibor@med.semmelweis-univ.hu.
Jazyk: angličtina
Zdroj: Prostate cancer and prostatic diseases [Prostate Cancer Prostatic Dis] 2023 Dec; Vol. 26 (4), pp. 665-672. Date of Electronic Publication: 2022 Dec 12.
DOI: 10.1038/s41391-022-00626-2
Abstrakt: Background: 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).
Methods: 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.
Results: 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.
Conclusions: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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