{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:10:56Z","timestamp":1789657856292,"version":"4.0.1"},"reference-count":26,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"\n Importance<\/jats:title>\n Progression-free survival (PFS) is a widely accepted primary end point in metastatic breast cancer (mBC) trials; however, it remains susceptible to assessment bias. To reduce this risk, blinded independent central review (BICR) is often incorporated into trial designs, but emerging evidence has suggested discordance between investigator- and BICR-assessed PFS.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To compare BICR- and investigator-assessed PFS of patients with hormone receptor\u2013positive\/\n ERBB2<\/jats:italic>\n -negative mBC.\n <\/jats:p>\n <\/jats:sec>\n \n Data Sources<\/jats:title>\n PubMed, Embase, CENTRAL, and major conference proceedings were searched from database inception to November 27, 2025, to identify all potential eligible studies.<\/jats:p>\n <\/jats:sec>\n \n Study Selection<\/jats:title>\n \n Phase 2 or 3 randomized clinical trials (RCTs) including patients with hormone receptor\u2013positive\/\n ERBB2<\/jats:italic>\n -negative mBC with progression following CDK4\/6 inhibitor therapy. Eligible studies required or permitted prior CDK4\/6 inhibitor use and reported PFS assessed by both local investigators and BICR.\n <\/jats:p>\n <\/jats:sec>\n \n Data Extraction and Synthesis<\/jats:title>\n Data from the eligible RCTs were extracted by 2 reviewers (L.V.R. and Z.B.). A trial-level random-effect meta-analysis was performed.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Outcomes were the discrepancy index (DI)\u2014the ratio of hazard ratios for BICR- vs investigator-assessed PFS\u2014and the absolute difference in median PFS between the 2 assessments.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 4989 identified records, 21 RCTs with 9165 patients met inclusion criteria. Eleven RCTs used BICR as the primary assessment, 13 were open label, and 7 required prior treatment with CDK4\/6 inhibitors as an inclusion criterion. No statistically significant difference was observed between investigator- and BICR-assessed PFS overall, with a DI of 1.02 (95% CI, 0.95-1.10;\n P<\/jats:italic>\n \u2009=\u2009.57), which was consistent across meta-regression analyses. The pooled PFS difference was 0.26 months (95% CI, \u22120.16 to 0.68 months;\n P<\/jats:italic>\n \u2009=\u2009.22) in interventional arms and 0.44 months (95% CI, 0.09-0.78 months;\n P<\/jats:italic>\n \u2009=\u2009.01) in control arms.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n Results of this systematic review and meta-analysis show that despite a trend toward longer median PFS with BICR in recent RCTs of patients with hormone receptor\u2013positive\/\n ERBB2<\/jats:italic>\n -negative mBC, there was no statistically significant DI between BICR- and investigator-assessed PFS. Results were consistent across meta-regression analyses and in outlier trials, suggesting that both approaches yield comparable PFS estimates.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.1571","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:01:00Z","timestamp":1784214060000},"page":"974","source":"Crossref","is-referenced-by-count":0,"title":["Progression-Free Survival in Metastatic Breast Cancer by Local Investigators vs Blinded Independent Central Review"],"prefix":"10.1001","volume":"12","author":[{"given":"Lis Victoria","family":"Ravani","sequence":"first","affiliation":[{"name":"University of Sao Paulo School of Medicine, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Bagheri","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Kalinsky","sequence":"additional","affiliation":[{"name":"Emory University, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold J.","family":"Burstein","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Bardia","sequence":"additional","affiliation":[{"name":"UCLA Health Jonsson Comprehensive Cancer Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason A.","family":"Mouabbi","sequence":"additional","affiliation":[{"name":"The University of Texas MD Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"O\u2019Regan","sequence":"additional","affiliation":[{"name":"University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth A.","family":"Wander","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"},{"name":"Massachusetts General Hospital Cancer Center, Boston"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"8","key":"coi260035r1","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1634\/theoncologist.2015-0366","article-title":"Clinical implications of the progression-free survival endpoint for treatment of hormone receptor-positive advanced breast cancer.","volume":"21","author":"Kaklamani","year":"2016","journal-title":"Oncologist"},{"issue":"22","key":"coi260035r2","doi-asserted-by":"publisher","first-page":"3791","DOI":"10.1200\/JCO.2008.16.1711","article-title":"Blinded independent central review of progression-free survival in phase III clinical trials: important design element or unnecessary 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