633 - Aflibercept/FOLFIRI (AF) vs placebo/FOLFIRI (PF) in metastatic colorectal cancer (mCRC): post-hoc analysis of survival excluding adjuvant (ADJ)-only...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Florence Joulain
Authors F. Joulain1, U. Iqbal2, F. Diamand3, E. Van Cutsem4, J. Tabernero5, C. Allegra6
  • 1Global Evidence And Value Development, Sanofi, Chilly Mazarin/FR
  • 2Research And Development, Sanofi, Cambridge/US
  • 3Evidence And Value Development, Keyrus Biopharma, Levallois-Perret/FR
  • 4Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven/BE
  • 5Oncology Department, Vall d'Hebron University HospitalMedical Oncology Service, ES-08035 - Barcelona/ES
  • 6Oncology, University of Florida, Gainesville/US

Abstract

Background

A small proportion of poor prognosis CRC patients (pts) treated with ADJ therapy relapse within 6 months of treatment, and progress to mCRC (Sargent JCO 2007;25:4569). The VELOUR phase III trial evaluated the novel fusion protein aflibercept (VEGF Trap) plus FOLFIRI in mCRC pts previously treated with oxaliplatin. In this study 10% of pts directly progressed from ADJ setting to first-line. Median and mean overall survival (OS) was determined for VELOUR pts excluding those that progressed directly from the ADJ setting.

Method

Baseline characteristics and efficacy were determined for the ITT pts excluding ADJ-only pts. Since some pts were alive at the time of final analysis, mean OS was estimated by extrapolating the trial Kaplan-Meier curve using a survival function. The goodness-of-fit of parametric distributions was evaluated by AIC, BIC criteria. Survival functions were fit to each treatment (TXT) arm separately or by combining the two arms and using TXT as a covariate to control for variation.

Results

Of 1226 pts enrolled in VELOUR, 60 (9.8%) AF pts and 64 (10.4%) pF pts received oxaliplatin in ADJ setting only. Excluding these pts, baseline characteristics remained similar between the 2 arms. Median age was 61 years, 60% of pts were male, 30% of pts were randomized in the prior bevacizumab stratum and very few pts had ECOG PS 2 (2.1%) as per IVRS. 43.6% of pts had 1 or less metastatic site at baseline and 25.4% had liver metastasis only. Median OS was significantly improved with AF vs pF (13.8 vs 11.9 months; adjusted HR = 0.80 [95% CI: 0.69 to 0.92]). For mean OS, the loglogistic function provided the best fit of the VELOUR data for the ITT population excluding ADJ-only pts both with and without TXT as covariate.

Conclusion

Excluding ADJ-only pts, the VELOUR trial increased median OS (1.9 vs 1.4) and mean OS (5.1 vs 4.7) with AF compared to pF, thus reinforcing the therapeutic benefit of AF in clinically relevant patient populations.

Table: 633

Median OS (months) Restricted Mean OS (months) over 15 years
AF (N = 552) pF (N = 550) Δ Δ ITT Loglogistic AF pF Δ Δ ITT
13.8 11.9 1.9 1.4 TXT group independently 22.7 17.6 5.1 4.7
TXT group as covariate 21.5 18.5 3.0 2.5
Disclosure

F. Joulain: I am an employee of Sanofi.

U. Iqbal: I am an employee of Sanofi.

F. Diamand: I am an employee of Sanofi.

E. Van Cutsem: I have received research funding from Sanofi.

J. Tabernero: I have an advisory relationship with Sanofi, Roche, and Regeneron.

C. Allegra: I have an advisory relationship with Sanofi.