{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T10:52:02Z","timestamp":1782816722315,"version":"3.54.5"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing.<\/jats:p><\/jats:sec>Objective<\/jats:title>To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA<\/jats:italic>-like genomic profile and patients without a tumor BRCA<\/jats:italic>-like profile.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cohort study was a secondary analysis of the PAOLA-1 randomized clinical trial that compared olaparib plus bevacizumab with placebo plus bevacizumab as maintenance treatment in patients with advanced high-grade ovarian cancer after a good response to first-line platinum with taxane chemotherapy plus bevacizumab, irrespective of germline or tumor BRCA1\/2<\/jats:italic> mutation status. All patients with available tumor DNA were included in the analysis. The current analysis tested for an interaction between BRCA<\/jats:italic>-like status and olaparib treatment on survival outcomes. The original trial was conducted between July 2015 and September 2017; at the time of data extraction for analysis in March 2022, a median follow-up of 54.1 months (IQR, 28.5-62.2 months) and a total follow-up time of 21\u202f711 months was available, with 336 PFS and 245 OS events.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Tumor homologous recombination deficiency was assessed using the BRCA<\/jats:italic>-like copy number aberration profile classifier. Myriad MyChoice CDx was previously measured. The trial was randomized between the olaparib and\u2009bevacizumab and placebo plus bevacizumab groups.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>This secondary analysis assessed hazard ratios (HRs) of olaparib vs placebo among biomarker strata and tested for interaction between BRCA<\/jats:italic>-like status and olaparib treatment on PFS and OS, using Cox proportional hazards regression.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 469 patients (median age, 60 [range 26-80] years) were included in this study. The patient cohort consisted of women with International Federation of Gynaecology and Obstetrics stage III (76%) high-grade serous (95%) ovarian cancer who had no evaluable disease or complete remission at initial or interval debulking surgery (76%). Thirty-one percent of the tumor samples (n\u2009=\u2009138) harbored a pathogenic BRCA<\/jats:italic> mutation, and BRCA<\/jats:italic>-like classification was performed for 442 patients. Patients with a BRCA<\/jats:italic>-like tumor had a longer PFS after olaparib treatment than after placebo (36.4 vs 18.6 months; HR, 0.49; 95% CI, 0.37-0.65; P<\/jats:italic>\u2009&amp;lt;\u2009.001). No association of olaparib with PFS was found in patients with a non\u2013BRCA<\/jats:italic>-like tumor (17.6 vs 16.6 months; HR, 1.02; 95% CI, 0.68-1.51; P<\/jats:italic>\u2009=\u2009.93). The interaction was significant (P<\/jats:italic>\u2009=\u2009.004), and HRs and P<\/jats:italic> values (for interaction) were similar in the relevant subgroups, OS, and multivariable analyses.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA<\/jats:italic>-like tumor, but not those with a non\u2013BRCA<\/jats:italic>-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-<\/jats:italic>like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.5552","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T15:00:59Z","timestamp":1712674859000},"page":"e245552","source":"Crossref","is-referenced-by-count":13,"title":["Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA<\/i>-Like Genomic Aberrations"],"prefix":"10.1001","volume":"7","author":[{"given":"Philip C.","family":"Schouten","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology, Medical Faculty, University Hospital Cologne, 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