PD-0022 Aflibercept Versus Placebo in Combination with Folfiri in Previously Treated Metastatic Colorectal Cancer: Mean Overall Survival for Subgroups from Velour

Abstract

ABSTRACT Introduction The VELOUR phase III trial evaluated the efficacy and safety of the novel fusion protein aflibercept (VEGF Trap) in combination with FOLFIRI in metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. Median overall survival (OS) showed significant improvement with 13.50 months in the aflibercept arm vs. 12.06 months in the placebo arm (p = 0.0032; HR = 0.82 [95.34% CI: 0.71 to 0.94]). Treatments were allocated through a 1:1 randomization stratified by ECOG PS (0, 1 or 2) and prior bevacizumab use. The purpose of this analysis was to estimate mean OS in ITT population and stratified subgroups of VELOUR for populating cost-effectiveness analysis. Methods Because some patients were alive at the time of the final analysis, mean OS must be estimated by extrapolating the trial Kaplan-Meier curve using a survival function. Five standard parametric distributions were tested: exponential, Weibull, lognormal, log-logistic and Gompertz. Akaike’s Information Criteria (AIC), Bayesian Information Criteria (BIC) and graphical methods were used to evaluate the goodness of fit of the distributions. Survival functions were fit to each treatment arm separately or by combining the two arms and using treatment as covariate to control for variation. Mean OS was estimated for the ITT population and stratification subgroups accordingly. The subgroup of patients with PS = 2 is not presented as it represents only 27 patients (2.2% of the 1226 ITT patients). Results The log-logistic function provided the best fit of the VELOUR data for the ITT population and for all subgroups except in the placebo arm for the PS = 0 subgroup and for the prior bevacizumab subgroup where the lognormal and Weibull distributions respectively fit best. Using the best fits, mean survival was greater in the aflibercept arm compared to placebo arm in all subgroups, by an amount ranging from 1.4 to 9.8 months. Conclusion These additional analyses of mean OS in the ITT population and stratification subgroups support the primary VELOUR analyses demonstrating a survival benefit across patient subgroups of Aflibercept/FOLFIRI over Placebo/FOLFIRI. These results have important implications in terms of informing consistent clinical and economic benefit of aflibercept across general, as well as clinically relevant patient subpopulations in second-line mCRC. Study NCT00561470 was funded by sanofi, in partnership with Regeneron. Table 1 .