Association between exposure to bevacizumab (BV) beyond first progression (BBP) and overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Results from a large observational study (BRiTE)
4036 Background: While BV prolongs OS when used with standard 1st- or 2nd-line chemotherapy (CT) in mCRC, no data exist on the effects of BBP. A previous report from BRiTE showed favorable median OS (27.1 mo, 95% CI 24.8-NE), with 1st line PFS (median 10.1 mo, 95% CI:9.7–10.4) comparable to historical mCRC trials, suggesting significant impact of post-progression survival on OS. This exploratory analysis evaluates the association of various pre- and post-treatment variables with OS in BRiTE. Methods: Pt population and methods have been described previously (Kozloff, ASCO 2006). All pts in BRiTE received BV as part of 1st-line therapy. The use of BBP and choice of CT were at investigator’s discretion. Kaplan-Meier methods were used to estimate PFS and OS. Cox’s proportional hazard model was used to assess the independent effects of pre- and post-treatment pt- related factors on OS, including age, ECOG PS, albumin, alkaline phosphatase, site of primary tumor, 1st-line CT regimen, 1st-line PFS, exposure to all 3 active CT agents, receipt of any 2nd-line CT, exposure to cetuximab, and BBP. Though there was variability observed in patterns of BBP, including continuous and discontinuous use, for the purpose of this analysis, BBP was defined as any exposure to BV after 1st progression (PD). Results: A total of 1,953 pts were treated in BRiTE. At median follow-up of 17.5 mo, there were 1,369 1st PD and 839 deaths. Among pts with 1st PD, 65.2% received any 2nd-line CT, 34.8% received cetuximab, and 53.8% received BBP. In a multivariate analysis, BBP and exposure to any 2nd-line CT were independently associated with increased OS (both p<0.0001). Age ≥65, PS ≥1, low albumin, elevated alkaline phosphatase, colon primary, and use of IFL were associated with inferior OS. Conclusions: BBP appears to be associated with longer OS in BRiTE. This finding supports the evaluation of BBP in prospective randomized clinical trials. Other factors that may have impacted this finding, including physician-related variables, will be investigated in future analyses. [Table: see text]