459P Progression-free survival (PFS) assessment by local investigators versus blinded independent central review (BICR) in randomized clinical trials (RCTs) in metastatic breast cancer (MBC): Is it really needed?

In RCTs, BICR is used to minimize the heterogeneity and risk of bias associated with radiological response evaluation by local investigators. However, BICR adds costs and complexity in trial management, which questions its practical utility. We aimed to assess the discrepancy index between PFS assessment by local investigators and by BICR in RCTs of MBC. A systematic search of PubMed, Embase, Cochrane databases and conference proceedings (ASCO, SABCS and ESMO meetings) was performed up to January 4, 2023. All RCTs published from 2000 to 2022, including MBC patients treated in first or second-line, and reporting PFS assessed by local investigators and BICR were included (PROSPERO - CRD42021229865). The agreement between hazard ratios (HRs) of PFS assessed by local investigators and BICR was measured using intraclass correlation coefficient (ICC). A discrepancy index, defined as the ratio of BICR-assessed HR by the corresponding investigator-assessed HR, was calculated for each trial to quantify the level of agreement in the estimated effect. A total of 24 studies with 13,338 patients were included in the analysis. Among them, 19 (79%) were in first line, 18 (75%) were phase III trials and 23 (96%) had PFS as primary endpoint. The overall combined discrepancy index was 0.97 (95%CI 0.85-1.10; ICC = 0.831, p-value <0.001) suggesting no statistically significant difference in PFS assessment by local investigators vs BICR. This result was consistent across all subgroups analyzed (the table).Table: 459PDiscrepancy index and 95% confidence intervals in the overall population and in subgroupsDiscrepancy index (95% CI)Overall0.97 (0.85-1.10)Line of treatmentFirst line0.98 (0.84-1.15)Second line0.94 (0.75-1.17)Study phasePhase II1.05 (0.66-1.66)Phase III0.96 (0.84-1.10)Study designDouble blind0.97 (0.83-1.13)Open label0.97 (0.78-1.21)BC subtypeHER2+0.96 (0.70-1.28)Luminal0.94 (0.67-1.30)TNBC0.96 (0.67-1.39)Study start yearBefore 20100.97 (0.83-1.13)After 20110.97 (0.77-1.21)RECIST1.00.97 (0.82-1.14)1.10.96 (0.78-1.18)PFS primary endpointYes0.97 (0.85-1.10)No0.87 (0.25-3.07) Open table in a new tab The good concordance between local investigator and BICR assessments supports the reliability of local investigator-assessed PFS as primary endpoint for RCTs in MBC. The resources used for BICR might be reallocated to other areas, such as translational research, decreasing the burden of clinical trial conduction.