Progression-Free Survival in Metastatic Breast Cancer by Local Investigators vs Blinded Independent Central Review: A Systematic Review and Meta-Analysis
In brief
Investigator and central review yield PFS results within 0.3 months
A meta-analysis of 21 phase 2/3 trials in hormone-receptor-positive, HER2-negative metastatic breast cancer found no significant difference between local investigator-assessed and blinded independent central review progression-free survival, with a pooled discrepancy of only about three-tenths of a month. The finding suggests either method can be used without materially biasing trial outcomes, though the small trend toward longer PFS with central review in control arms warrants further scrutiny.
- Journal
- JAMA oncology (Q1)
- Published
- 16 July 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Lis Victoria Ravani, Zahra Bagheri, Kevin Kalinsky, Harold J Burstein, Aditya Bardia, Jason A Mouabbi, et al.
- PMID
- 42461660
- DOI
- 10.1001/jamaoncol.2026.1571
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (top studies of the week, 19 July 2026): SR/MA of PFS vs BICR in metastatic breast cancer
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.