Poly (ADP-ribose) polymerase inhibitors (PARPi) represent an option in selected cases of metastatic castration-resistant prostate cancer (mCRPC). The aim of the present systematic review and meta-analysis is to evaluate the efficacy and safety of approved (Olaparib, Rucaparib) and investigational (Talazoparib, Niraparib, Veliparib) PARPi in mCRPC patients.
Three databases were queried for studies analyzing oncological outcomes and adverse events of mCRPC patients receiving PARPi. Primary outcome was a PSA decline ≥ 50% from baseline. Secondary outcomes were objective response rate, progression-free survival (PFS), radiological PFS, overall survival (OS), conversion of circulating tumor cell count, and time to PSA progression. The number and rate of any grade adverse events (AEs), grade ≥ 3 AEs, and most common grade ≥ 3 AEs were registered. A subanalysis of outcomes per mutation type, prospective trials, and studies adopting combination therapies was performed. Overall, 31 studies were included in this systematic review, 28 of which are available for meta-analysis. The most frequently investigated drug was Olaparib. The most frequent mutation was BRCA2. A PSA decline rate of 43% (95% CI 0.32-0.54) was observed in the overall population. Mean OS was 15.9 (95% CI 12.9-19.0) months. In BRCA2 patients, PSA decline rate was 66% (95% CI 0.57-0.7) and OS 23.4 months (95% CI 22.8-24.1). Half of the patients suffered from grade 3 and 4 AEs (0.50 [95% CI 0.39-0.60]). Most common AEs were hematological, the most frequent being anemia (21.5%). PARP inhibitors represent a viable option for mCRPC patients. Current evidence suggests an increased effectiveness in homologous recombination repair (HRR) gene mutation carriers, especially BRCA2.
Clinical genitourinary cancer. 2023 Dec 21 [Epub ahead of print]
Francesco Ditonno, Alberto Bianchi, Sarah Malandra, Antonio Benito Porcaro, Emanuela Fantinel, Riccardo Negrelli, Matteo Ferro, Michele Milella, Matteo Brunelli, Riccardo Autorino, Maria Angela Cerruto, Alessandro Veccia, Alessandro Antonelli
Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) Verona, Verona, Italy; Department of Urology, Rush University, Chicago, IL, USA., Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) Verona, Verona, Italy., Department of Surgery, Dentistry, Pediatrics and Ginecology, University of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) Verona, Verona, Italy., Section of Oncology, Department of Medicine, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Department of Radiology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy., Department of Urology, European Institute of Oncology (IEO) IRCCS, Milan, Italy., Department of Diagnostic and Public Health, Section of Pathology, University of Verona, Italy., Department of Urology, Rush University, Chicago, IL, USA., Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) Verona, Verona, Italy. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/38281877