{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:57:55Z","timestamp":1791464275673,"version":"4.3.4"},"reference-count":49,"publisher":"American Medical Association (AMA)","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n \n First-line maintenance therapy with poly(adenosine diphosphate-ribose) polymerase inhibitors (PARP inhibitors) after platinum-based chemotherapy improves progression-free survival (PFS) in advanced epithelial ovarian cancer (EOC), particularly in patients with\n BRCA<\/jats:italic>\n -variant or homologous recombination-deficient tumors. However, overall survival (OS) benefits remain uncertain, and toxic effect profiles emphasize the need for optimized patient and agent selection.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the efficacy and safety of first-line PARP inhibitor maintenance therapy compared with chemotherapy alone in advanced-stage EOC, with subgroup analyses by\n BRCA<\/jats:italic>\n and HRD status, up-front or interval surgery, chemotherapy response, and residual disease.\n <\/jats:p>\n <\/jats:sec>\n \n Data sources<\/jats:title>\n Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from database inception to August 19, 2024.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n Randomized clinical trials and prospective 2-arm studies evaluating PARP inhibitor maintenance therapy in patients with advanced-stage EOC responding to first-line platinum-based chemotherapy were included.<\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed in reporting this study. Data were independently extracted by 2 reviewers. Random-effects models were used for meta-analysis. Risk of bias was assessed with Cochrane risk of bias and certainty of evidence with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcomes were PFS and OS; secondary outcomes included high-grade adverse events.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 7 randomized clinical trials with 4013 patients with advanced-stage epithelial ovarian cancer responding to first-line platinum-based chemotherapy were included. PARP inhibitor maintenance was associated with improved PFS in the overall population (hazard ratio [HR], 0.57; 95% CI, 0.46-0.70; high certainty) and in all molecular subgroups except the homologous recombination proficient group (\n BRCA<\/jats:italic>\n variant: HR, 0.40; 95% CI, 0.35-0.45;\n BRCA<\/jats:italic>\n wild type: HR, 0.62; 95% CI, 0.44-0.86; homologous recombination deficient: HR, 0.44; 95% CI, 0.39-0.50; all high certainty). PFS benefits were consistent across surgical timing, chemotherapy responses, and residual disease; for example, surgical timing had HRs of 0.51 (95% CI, 0.31-0.84) for neoadjuvant chemotherapy and 0.54 (95% CI, 0.36-0.81) for primary cytoreductive surgery (all high certainty). No molecular subgroup showed a statistically significant OS improvement (high to low certainty). High-grade adverse events were more common in the PARP inhibitor group (HR, 2.40; 95% CI, 1.16-4.93; high certainty). Observed treatment efficacy and toxic effects varied across PARP inhibitor regimens; for example, the risk ratio for any recurrence or death in the overall study group ranged from 0.53 (95% CI, 0.40-0.70) for senaparib to 0.83 (95% CI, 0.68-1.00) for olaparib, while the risk ratio for high-grade adverse events ranged from 1.15 (95% CI, 0.64-2.06) for veliparib to 4.73 (95% CI, 2.77-8.07) for niraparib.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n In this study, no subgroup showed an association between first-line PARP inhibitor maintenance therapy in advanced-stage EOC and improved OS, and findings suggest that the consistency of associated PFS benefits may vary, particularly in homologous recombination proficient and\n BRCA<\/jats:italic>\n wild type tumors. Variability in efficacy and toxic effects across subgroups and PARP inhibitor regimens underscores the importance of individualized treatment decisions.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.41648","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T16:00:24Z","timestamp":1762358424000},"page":"e2541648","source":"Crossref","is-referenced-by-count":21,"title":["PARP Inhibitor Maintenance After First-Line Chemotherapy in Advanced-Stage Epithelial Ovarian Cancer"],"prefix":"10.1001","volume":"8","author":[{"given":"Stamatios","family":"Petousis","sequence":"first","affiliation":[{"name":"Second Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilker","family":"Kahramanoglu","sequence":"additional","affiliation":[{"name":"Department of Gynaecologic Oncology, Biruni University, Istanbul, 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