Independent review of E2100 progression-free survival (PFS) with the addition of bevacizumab (B) to paclitaxel (P) as initial chemotherapy for metastatic breast cancer (MBC)

Abstract

1036 Background: E2100 was an open-label, multi-center, randomized, Phase III trial comparing P to P+B as initial chemotherapy for MBC. The original analysis based on investigator-assessed progression found a significant improvement in PFS (HR 0.498, p <0.001) (K. Miller, PASCO '05). A retrospective independent review of blinded radiological and clinical data was conducted to confirm the results. Methods: Radiographic images and physical exam findings were provided to the independent review facility (IRF; RadPharm Inc.) who reviewed these data in a blinded fashion, in accordance with a prespecified IRF charter following the RECIST criteria. PFS was reanalyzed as an intent-to-treat analysis of all 722 randomized subjects, and included on-study deaths and progression events assessed by the IRF that occurred on or before Feb 9, 2005 (consistent with the data cut-off for the original interim analysis). PFS was also reanalyzed using investigator assessments but otherwise following the same analysis methods. Results: Images were submitted for review for 89.9% of patients. Missing data were balanced between the two treatment arms. Eight planned sensitivity analyses that tested the impact of non-protocol therapy, missing data, and informative censoring in the assessment of progression for individual patients were conducted; all retained statistical significance for the addition of bevacizumab. Conclusions: The PFS risk was reduced by more than half and the ORR more than doubled with the addition of bevacizumab to weekly paclitaxel in both analyses, confirming the substantial and robust bevacizumab treatment effect. The strong consistency of the IRF and Investigator based PFS and ORR results validate original data reported by ECOG in this open-label trial. IRF Assessed Investigator Assessed P N=354 P+B N=368 P N=354 P+B N=368 Progression-free survival (HR) 0.483 0.421 p value (log-rank) <0.0001 <0.0001 Median (months) 5.8 11.3 5.8 11.4 Objective response in patients with measurable disease at baseline (%) 22.2 49.8 23.4 48.0 p value <0.0001 <0.0001 HR=hazard ratio Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc., Roche Amgen, Genentech, Inc., Gilead Sciences Genentech, Inc. Genentech, Inc.