Aflibercept Versus Placebo In Combination With Folfiri In Previously Treated Metastatic Colorectal Cancer (Mcrc): Mean Overall Survival (Os) Estimation From A Phase Iii Trial (Velour).

3602 Background: VELOUR evaluated the efficacy and safety of the novel fusion protein aflibercept (VEGF Trap) in combination with FOLFIRI in mCRC patients previously treated with oxaliplatin. Median OS showed significant improvement with 12.06 months in placebo arm vs 13.50 months in aflibercept arm (p=0.0032; HR=0.82 [95.34% CI: 0.71 to 0.94]) [Van Cutsem, 2011]. Since survival data in oncology are usually right skewed, median survival is preferred for regulatory purposes. However, mean survival estimation can render a more meaningful estimate for long term benefit of interventions, and be effectively applied to clinical and economic decision support. Estimating mean OS also allows payers to derive an estimation of total costs and outcomes in the population. The purpose of this study was to estimate the mean OS for VELOUR trial. Methods: During the trial follow-up period, mean OS is not observable and can be estimated by extrapolating the trial Kaplan-Meier curve using a survival function. Several standard parametric distributions were tested: exponential, weibull, lognormal, loglogistic and gompertz. Akaike’s Information Criteria (AIC), Bayesian Information Criteria (BIC) and graphical method were used to evaluate the goodness of fit of the distributions. Models were run by treatment arm separately or combining the two arms and using treatment as covariate to control for variation. Results: Using AIC/BIC and graphical method, loglogistic function best fit the VELOUR data both with and without treatment as covariate. Weibull distribution is used for sensitivity analysis. Conclusions: Using loglogistic function, mean OS benefit for aflibercept in combination with FOLFIRI is at least 2.9 months (versus 1.4 months difference in median survival). The results have important implications for clinical and economic decision support. Study NCT00561470 was funded by sanofi, in partnership with Regeneron. [Table: see text]