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Randomized Controlled Trial
. 2013 Oct 1;109(7):1735-43.
doi: 10.1038/bjc.2013.523. Epub 2013 Sep 17.

Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer

F Joulain  1 , I Proskorovsky, C Allegra, J Tabernero, M Hoyle, S U Iqbal, E Van Cutsem
Affiliations
Randomized Controlled Trial

Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer

F Joulain et al. Br J Cancer. .

Abstract

Background: Mean survival in cancer trials can be estimated with statistical techniques to extrapolate study survival curves. This methodology was applied to data from the VELOUR trial, where use of the novel biologic aflibercept (ziv-aflibercept in the United States) in combination with fluorouracil+leucovorin+irinotecan (FOLFIRI), had significantly increased median overall survival (OS) by 1.44 months, vs placebo plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) resistant to, or that had progressed following, an oxaliplatin-containing regimen.

Methods: Parametric survival analyses were used to identify distributions with the best fit to the empirical VELOUR data. Mean OS for the two treatment groups (and pre-defined subgroups) was calculated from the fitted curves over a 15-year survival period.

Results: Overall, the log-logistic distribution was the best-fitting for both treatment arms and, with it, the estimated difference in mean OS over 15 years between aflibercept+FOLFIRI and placebo+FOLFIRI was 4.7 months. In addition, the survival advantage with aflibercept was at least 3 months for the ITT population, whichever distribution was used to extrapolate survival.

Conclusion: Extrapolation of survival curves suggests the mean OS difference for aflibercept in the VELOUR trial is at least 3 months in the ITT population and selected subgroups.

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Figures

Figure 1
Figure 1
(A) Observed vs predicted OS (aflibercept ITT Population). (B) Observed vs predicted OS (placebo ITT population).
Figure 2
Figure 2
(A) Observed vs predicted OS for pre-defined subgroups of interest (aflibercept). (B) Observed vs predicted OS for pre-defined subgroups of interest (placebo).
Figure 3
Figure 3
Long-term predictions for ITT: log-logistic vs Weibull fitted separately.
Figure 4
Figure 4
Long-term predictions for pre-defined subgroups of interest: log-logistic vs Weibull fitted separately.
See this image and copyright information in PMC

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