Importance 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. Objective To compare BICR- and investigator-assessed PFS of patients with hormone receptor–positive/ ERBB2 -negative mBC. Data Sources PubMed, Embase, CENTRAL, and major conference proceedings were searched from database inception to November 27, 2025, to identify all potential eligible studies. Study Selection Phase 2 or 3 randomized clinical trials (RCTs) including patients with hormone receptor–positive/ ERBB2 -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. Data Extraction and Synthesis 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. Main Outcomes and Measures Outcomes were the discrepancy index (DI)—the ratio of hazard ratios for BICR- vs investigator-assessed PFS—and the absolute difference in median PFS between the 2 assessments. Results 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; P = .57), which was consistent across meta-regression analyses. The pooled PFS difference was 0.26 months (95% CI, −0.16 to 0.68 months; P = .22) in interventional arms and 0.44 months (95% CI, 0.09-0.78 months; P = .01) in control arms. Conclusions and Relevance 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–positive/ ERBB2 -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.
Ravani et al. (Thu,) studied this question.