Efficacy and safety of PARP inhibitors in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis of clinical trials.
Efficacy
Meta-analysis
PARP inhibitors
Prostate cancer
Safety
Systematic review
Journal
Cancer treatment reviews
ISSN: 1532-1967
Titre abrégé: Cancer Treat Rev
Pays: Netherlands
ID NLM: 7502030
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
16
06
2023
revised:
04
09
2023
accepted:
06
09
2023
pmc-release:
01
11
2024
medline:
23
10
2023
pubmed:
17
9
2023
entrez:
16
9
2023
Statut:
ppublish
Résumé
PARP inhibitors (PARPi) are a standard-of-care (SoC) treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Several clinical trials have shown the potential of combining PARPi with other anticancer agents. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the efficacy and safety of PARPi in patients with metastatic prostate cancer. MEDLINE, Cochrane CENTRAL, EMBASE, CINAHL, and Web of Science were searched on March 22nd, 2023, for phase 2 or 3 clinical trials. Efficacy (progression-free survival [PFS], overall survival [OS], PSA decline >50% [PSA50], and objective response rate [ORR]) and safety outcomes were assessed in the included studies. Seventeen clinical trials (PARPi monotherapy [n = 7], PARPi + androgen-receptor signaling inhibitors [ARSI] [n = 6], and PARPi + immune checkpoint inhibitors [ICI] [n = 4]) were included in the quantitative analyses. PARPi monotherapy improved radiographic PFS and OS over SoC in mCRPC patients with alterations in BRCA1 or BRCA2 genes but not in those with alterations in the ATM gene. Higher rates of PSA50 and ORR were reported in participants treated with PARPi + ARSI than in single-agent PARPi or PARPi + ICI. Although the rate of high-grade adverse events was similar across all groups, treatment discontinuation was higher in patients treated with PARPi-based combinations than PARPi monotherapy. The efficacy of PARPi is not uniform across mCRPC patients with alterations in DNA damage repair genes, and optimal patient selection remains a clinical challenge. No unexpected safety signals for this class of agents emerged from this analysis.
Identifiants
pubmed: 37716332
pii: S0305-7372(23)00116-0
doi: 10.1016/j.ctrv.2023.102623
pmc: PMC10591840
mid: NIHMS1931913
pii:
doi:
Substances chimiques
Poly(ADP-ribose) Polymerase Inhibitors
0
Immune Checkpoint Inhibitors
0
Types de publication
Meta-Analysis
Systematic Review
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
102623Subventions
Organisme : Intramural NIH HHS
ID : Z99 CA999999
Pays : United States
Informations de copyright
Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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