{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:14:02Z","timestamp":1786972442226,"version":"build-2736575974"},"reference-count":29,"publisher":"American Medical Association (AMA)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"\n Importance<\/jats:title>\n \n The BRIGHT-2 interim analysis demonstrated the efficacy of bireociclib plus fulvestrant in hormone receptor (HR)\u2013positive, human epidermal growth factor receptor 2 (\n ERBB2<\/jats:italic>\n ; previously\n HER2<\/jats:italic>\n )\u2013negative advanced breast cancer (ABC) after endocrine therapy progression. This final analysis includes an additional 11-month follow-up.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the efficacy and safety of bireociclib plus fulvestrant in HR-positive,\n ERBB2<\/jats:italic>\n -negative ABC.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This double-blind, placebo-controlled phase 3 randomized clinical trial was conducted at 64 hospitals in China between December 8, 2021, and October 24, 2022. Patients were enrolled and randomly assigned in a 2:1 to receive bireociclib plus fulvestrant or placebo plus fulvestrant. Data were analyzed from April 2024 to December 2025.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Patients received bireociclib, 360 mg, or placebo orally every 12 hours in combination with fulvestrant, 500 mg, intramuscularly (days 1 and 15 of cycle 1, then day 1 of each 28-day cycle).<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival, objective response rate, duration of response, and safety.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 305 included patients, the mean (SD) age was 54.1 (10.2) years, and the median (IQR) follow-up at data cutoff was 19 (18.5-19.6) months. Patients were randomized to bireociclib plus fulvestrant (n\u2009=\u2009204) or placebo plus fulvestrant (n\u2009=\u2009101); 275 (90.2%) had measurable disease and 268 (87.9%) had received prior systemic chemotherapy. Bireociclib plus fulvestrant significantly prolonged PFS vs placebo (median PFS, 14.7 months [95% CI, 11.1-20.2] vs 7.3 months [95% CI, 5.5-11.0]; hazard ratio, 0.54; 95% CI, 0.40-0.74;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). The objective response rate was higher (45.6% [95% CI, 38.6-52.7] vs 14.9% [95% CI, 8.6-23.3]) in the bireociclib group, with a prolonged median duration compared with placebo (not reached [95% CI, 11.1 to not reached] vs 13.1 months [95% CI, 10.2 to not reached]). Safety was consistent with the interim findings and the profiles of known cyclin-dependent kinase 4\/6 inhibitors. Subgroup analyses across multiple patient characteristics (menopausal status, metastatic sites, prior treatment, disease-free interval,\n ESR1<\/jats:italic>\n \/\n PIK3CA<\/jats:italic>\n \/\n TP53<\/jats:italic>\n alterations and others) showed consistent PFS improvements with bireociclib vs placebo. Patients with early-onset diarrhea appeared to derive more benefit from bireociclib (hazard ratio, 0.49; 95% CI, 0.36-0.68).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n The final analysis of the BRIGHT-2 randomized clinical trial confirms improved PFS with the addition of bireociclib to fulvestrant, with manageable safety as a treatment option for patients with HR-positive,\n ERBB2<\/jats:italic>\n -negative ABC with progression after prior endocrine therapy.\n <\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05077449<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.0318","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:30:35Z","timestamp":1773934235000},"page":"488","source":"Crossref","is-referenced-by-count":4,"title":["Bireociclib Plus Fulvestrant in Advanced Breast Cancer After Endocrine Progression"],"prefix":"10.1001","volume":"12","author":[{"given":"Jiayu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology and State Key Laboratory of Molecular Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Breast & Lymphoma, Harbin Medical University Cancer Hospital, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Peking University Cancer Hospital and Institute, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongsheng","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quchang","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hunan Cancer Hospital, Changsha, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuee","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshuai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Provincial Clinical Research Center for Breast Cancer, Wuhan Clinical Research Center for Breast Cancer, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Jining No. 1 People\u2019s Hospital, Jining, 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