PMID- 38281877
OWN - NLM
STAT- MEDLINE
DCOM- 20240311
LR  - 20240410
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Linking)
VI  - 22
IP  - 2
DP  - 2024 Apr
TI  - PARP Inhibitors in Metastatic Prostate Cancer: A Comprehensive Systematic Review 
      and Meta-analysis of Existing Evidence.
PG  - 402-412.e17
LID - S1558-7673(23)00277-X [pii]
LID - 10.1016/j.clgc.2023.12.011 [doi]
AB  - 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.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Ditonno, Francesco
AU  - Ditonno F
AD  - Department of Urology, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata (AOUI) Verona, Verona, Italy; Department of Urology, Rush University, 
      Chicago, IL, USA.
FAU - Bianchi, Alberto
AU  - Bianchi A
AD  - Department of Urology, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata (AOUI) Verona, Verona, Italy.
FAU - Malandra, Sarah
AU  - Malandra S
AD  - Department of Surgery, Dentistry, Pediatrics and Ginecology, University of 
      Verona, Azienda Ospedaliera Universitaria Integrata (AOUI) Verona, Verona, Italy.
FAU - Porcaro, Antonio Benito
AU  - Porcaro AB
AD  - Department of Urology, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata (AOUI) Verona, Verona, Italy.
FAU - Fantinel, Emanuela
AU  - Fantinel E
AD  - Section of Oncology, Department of Medicine, University of Verona, Azienda 
      Ospedaliera Universitaria Integrata, Verona, Italy.
FAU - Negrelli, Riccardo
AU  - Negrelli R
AD  - Department of Radiology, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata, Verona, Italy.
FAU - Ferro, Matteo
AU  - Ferro M
AD  - Department of Urology, European Institute of Oncology (IEO) IRCCS, Milan, Italy.
FAU - Milella, Michele
AU  - Milella M
AD  - Section of Oncology, Department of Medicine, University of Verona, Azienda 
      Ospedaliera Universitaria Integrata, Verona, Italy.
FAU - Brunelli, Matteo
AU  - Brunelli M
AD  - Department of Diagnostic and Public Health, Section of Pathology, University of 
      Verona, Italy.
FAU - Autorino, Riccardo
AU  - Autorino R
AD  - Department of Urology, Rush University, Chicago, IL, USA.
FAU - Cerruto, Maria Angela
AU  - Cerruto MA
AD  - Department of Urology, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata (AOUI) Verona, Verona, Italy.
FAU - Veccia, Alessandro
AU  - Veccia A
AD  - Department of Urology, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata (AOUI) Verona, Verona, Italy. Electronic address: a.veccia88@gmail.com.
FAU - Antonelli, Alessandro
AU  - Antonelli A
AD  - Department of Urology, University of Verona, Azienda Ospedaliera Universitaria 
      Integrata (AOUI) Verona, Verona, Italy.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
DEP - 20231221
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Poly(ADP-ribose) Polymerase Inhibitors)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Poly(ADP-ribose) Polymerase Inhibitors/adverse effects
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology
MH  - Prostate-Specific Antigen
MH  - Prospective Studies
MH  - Mutation
OTO - NOTNLM
OT  - Meta-analysis
OT  - Metastatic castration-resistant prostate cancer
OT  - Oncological outcomes
OT  - Safety
OT  - Systematic review
EDAT- 2024/01/29 00:42
MHDA- 2024/03/11 06:44
CRDT- 2024/01/28 21:53
PHST- 2023/09/15 00:00 [received]
PHST- 2023/12/05 00:00 [revised]
PHST- 2023/12/16 00:00 [accepted]
PHST- 2024/03/11 06:44 [medline]
PHST- 2024/01/29 00:42 [pubmed]
PHST- 2024/01/28 21:53 [entrez]
AID - S1558-7673(23)00277-X [pii]
AID - 10.1016/j.clgc.2023.12.011 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2024 Apr;22(2):402-412.e17. doi: 
      10.1016/j.clgc.2023.12.011. Epub 2023 Dec 21.