PMID- 38409030 OWN - NLM STAT- MEDLINE DCOM- 20240228 LR - 20240229 IS - 1757-2215 (Electronic) IS - 1757-2215 (Linking) VI - 17 IP - 1 DP - 2024 Feb 26 TI - PARP inhibitor era in ovarian cancer treatment: a systematic review and meta-analysis of randomized controlled trials. PG - 53 LID - 10.1186/s13048-024-01362-y [doi] LID - 53 AB - BACKGROUND: Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer. METHODS: This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses. RESULTS: In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29-0.40), BRCA mutant (HR 0.24, CI 0.18-0.31), germline BRCA mutant (HR 0.23, CI 0.18-0.30), and BRCA wild-type cases (HR 0.50, CI 0.39-0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51-0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30-0.71) and the BRCAm population (HR 0.36, CI 0.29-0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases. CONCLUSIONS: PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated. CI - (c) 2024. The Author(s). FAU - Baradacs, Istvan AU - Baradacs I AD - Department of Obstetrics and Gynecology, Semmelweis University, Ulloi ut 78/A, Budapest, H-1082, Hungary. AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. FAU - Teutsch, Brigitta AU - Teutsch B AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. AD - Institute for Translational Medicine, Szentagothai Research Centre, Medical School, University of Pecs, Pecs, Hungary. FAU - Varadi, Alex AU - Varadi A AD - Institute for Translational Medicine, Szentagothai Research Centre, Medical School, University of Pecs, Pecs, Hungary. FAU - Bila, Alexandra AU - Bila A AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. AD - School of Medicine, Semmelweis University, Budapest, Hungary. FAU - Vincze, Adam AU - Vincze A AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. AD - School of Medicine, Semmelweis University, Budapest, Hungary. FAU - Hegyi, Peter AU - Hegyi P AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. AD - Institute for Translational Medicine, Szentagothai Research Centre, Medical School, University of Pecs, Pecs, Hungary. AD - Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary. FAU - Fazekas, Tamas AU - Fazekas T AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. AD - Department of Urology, Semmelweis University, Budapest, Hungary. FAU - Komoroczy, Balazs AU - Komoroczy B AD - Department of Obstetrics and Gynecology, Semmelweis University, Ulloi ut 78/A, Budapest, H-1082, Hungary. AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. FAU - Nyirady, Peter AU - Nyirady P AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. AD - Department of Urology, Semmelweis University, Budapest, Hungary. FAU - Acs, Nandor AU - Acs N AD - Department of Obstetrics and Gynecology, Semmelweis University, Ulloi ut 78/A, Budapest, H-1082, Hungary. AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. FAU - Banhidy, Ferenc AU - Banhidy F AD - Department of Obstetrics and Gynecology, Semmelweis University, Ulloi ut 78/A, Budapest, H-1082, Hungary. AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. FAU - Lintner, Balazs AU - Lintner B AD - Department of Obstetrics and Gynecology, Semmelweis University, Ulloi ut 78/A, Budapest, H-1082, Hungary. lintnerster@gmail.com. AD - Centre for Translational Medicine, Semmelweis University, Budapest, Hungary. lintnerster@gmail.com. LA - eng GR - UNKP-22-3/New National Excellence Program/ GR - UNKP-22-3/New National Excellence Program/ PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20240226 PL - England TA - J Ovarian Res JT - Journal of ovarian research JID - 101474849 RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 0 (Antineoplastic Agents) SB - IM MH - Humans MH - Female MH - Poly(ADP-ribose) Polymerase Inhibitors/pharmacology/therapeutic use MH - Neoplasm Recurrence, Local/drug therapy MH - Randomized Controlled Trials as Topic MH - *Antineoplastic Agents/therapeutic use MH - *Ovarian Neoplasms/drug therapy/chemically induced MH - Carcinoma, Ovarian Epithelial/drug therapy PMC - PMC10895809 OTO - NOTNLM OT - HRD OT - Homologous recombination repair OT - Niraparib OT - Olaparib OT - Rucaparib COIS- The authors declare no competing interests. EDAT- 2024/02/27 00:42 MHDA- 2024/02/28 06:44 PMCR- 2024/02/26 CRDT- 2024/02/26 23:40 PHST- 2023/02/27 00:00 [received] PHST- 2024/01/31 00:00 [accepted] PHST- 2024/02/28 06:44 [medline] PHST- 2024/02/27 00:42 [pubmed] PHST- 2024/02/26 23:40 [entrez] PHST- 2024/02/26 00:00 [pmc-release] AID - 10.1186/s13048-024-01362-y [pii] AID - 1362 [pii] AID - 10.1186/s13048-024-01362-y [doi] PST - epublish SO - J Ovarian Res. 2024 Feb 26;17(1):53. doi: 10.1186/s13048-024-01362-y.