PMID- 38138301 OWN - NLM STAT- MEDLINE DCOM- 20231225 LR - 20231225 IS - 1648-9144 (Electronic) IS - 1010-660X (Print) IS - 1010-660X (Linking) VI - 59 IP - 12 DP - 2023 Dec 18 TI - Poly (ADP-ribose) Polymerase Inhibitors in Patients with Metastatic Castration-Resistant Prostate Cancer: A Meta-Analysis of Randomized Controlled Trials. LID - 10.3390/medicina59122198 [doi] LID - 2198 AB - Context: Several recent randomized controlled trials (RCTs) have reported on the survival benefits of poly (ADP-ribose) polymerase inhibitors (PARPi) compared to standard-of-care (SOC) treatment (enzalutamide, abiraterone, or docetaxel) in patients with metastatic castration-resistant prostate cancer (mCRPC). However, there is a limited integrated analysis of high-quality evidence comparing the efficacy and safety of PARPi and SOC treatments in this context. Objective: This study aims to comprehensively analyze the survival benefits and adverse events associated with PARPi and SOC treatments through a head-to-head meta-analysis in mCRPC. Evidence acquisition: A systematic review search was conducted in PubMed, Embase, Clinical trials, and the Central Cochrane Registry in July 2023. RCTs were assessed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The systematic review was prospectively registered on PROSPERO (CRD42023441034). Evidence synthesis: A total of 8 studies, encompassing 2341 cases in the PARPi treatment arm and 1810 cases in the controlled arm, were included in the qualitative synthesis. The hazard ratio (HR) for radiographic progression-free survival (rPFS) and overall survival (OS) were 0.74 (95% CI, 0.61-0.90) and 0.89 (95% CI, 0.80-0.99), respectively, in the intention-to-treatment patients. For subgroup analysis, HRs for rPFS and OS in the BRCA-mutated subgroup were 0.39 (95% CI, 0.28-0.55) and 0.62 (95% CI, 0.38-0.99), while in the HRR-mutated subgroup, HR for rPFS was 0.57 (95% CI, 0.48-0.69) and for OS was 0.77 (95% CI, 0.64-0.93). The odds ratio (OR) for all grades of adverse events (AEs) and AEs with severity of at least grade 3 were 3.86 (95% CI, 2.53-5.90) and 2.30 (95% CI, 1.63-3.26), respectively. Conclusions: PARP inhibitors demonstrate greater effectiveness than SOC treatments in HRR/BRCA-positive patients with mCRPC. Further research is required to explore ways to reduce adverse event rates and investigate the efficacy of HRR/BRCA-negative patients. FAU - Chao, Zheng AU - Chao Z AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Wang, Zefeng AU - Wang Z AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430030, China. FAU - Li, Le AU - Li L AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Jiang, Yi AU - Jiang Y AD - Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Tang, Yunxing AU - Tang Y AD - Department of Interventional Radiology and Vascular Surgery, Peking University First Hospital, Beijing 100034, China. FAU - Wang, Yanan AU - Wang Y AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Hao, Xiaodong AU - Hao X AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Zhang, Chunyu AU - Zhang C AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Guo, Xiangdong AU - Guo X AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. FAU - Yu, Weimin AU - Yu W AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430030, China. FAU - Cheng, Fan AU - Cheng F AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan 430030, China. FAU - Wang, Zhihua AU - Wang Z AD - Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20231218 PL - Switzerland TA - Medicina (Kaunas) JT - Medicina (Kaunas, Lithuania) JID - 9425208 RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 681HV46001 (Ribose) SB - IM MH - Male MH - Humans MH - *Poly(ADP-ribose) Polymerase Inhibitors/adverse effects MH - *Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology MH - Ribose/therapeutic use MH - Disease-Free Survival MH - Randomized Controlled Trials as Topic PMC - PMC10744677 OTO - NOTNLM OT - PARP inhibitors OT - adverse events OT - meta-analysis OT - prostate cancer OT - survival COIS- Zhihua Wang certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (e.g., employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. EDAT- 2023/12/23 12:44 MHDA- 2023/12/25 06:42 PMCR- 2023/12/18 CRDT- 2023/12/23 01:15 PHST- 2023/10/19 00:00 [received] PHST- 2023/12/07 00:00 [revised] PHST- 2023/12/15 00:00 [accepted] PHST- 2023/12/25 06:42 [medline] PHST- 2023/12/23 12:44 [pubmed] PHST- 2023/12/23 01:15 [entrez] PHST- 2023/12/18 00:00 [pmc-release] AID - medicina59122198 [pii] AID - medicina-59-02198 [pii] AID - 10.3390/medicina59122198 [doi] PST - epublish SO - Medicina (Kaunas). 2023 Dec 18;59(12):2198. doi: 10.3390/medicina59122198.