Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown.
To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC.
Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians.
We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively.
Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence.
In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.
European urology oncology. 2023 Sep 16 [Epub ahead of print]
Tamás Fazekas, Ádám D Széles, Brigitta Teutsch, Anita Csizmarik, Bálint Vékony, Tamás Kói, Nándor Ács, Péter Hegyi, Boris Hadaschik, Péter Nyirády, Tibor Szarvas
Department of Urology, Semmelweis University, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary., Department of Urology, Semmelweis University, Budapest, Hungary., Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Department of Stochastics, Institute of Mathematics, Budapest University of Technology and Economics, Budapest, Hungary., Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary., Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Institute of Pancreatic Diseases, 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; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/37722977
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