581P - Sensitivity analyses of progression-free survival (PFS) of aflibercept-FOLFIRI versus placebo-FOLFIRI in metastatic colorectal cancer (mCRC): result...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Eric Van Cutsem
Authors E. Van Cutsem1, J. Tabernero2, R. Lakomy3, J. Prausova4, P. Ruff5, V. Moiseyenko6, D. Ferry7, E. Boelle8, J. McKendrick9, C. Allegra10
  • 1Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven/BE
  • 2Oncology Department, Vall d'Hebron University HospitalMedical Oncology Service, ES-08035 - Barcelona/ES
  • 3Masaryk Memorial Cancer Institute, 65653 - Brno/CZ
  • 4Oncology, University Hospital Motol, Prague/CZ
  • 5Medical Oncology, University of WitwatersrandMedical School, ZA-2193 - Johannesburg/ZA
  • 6Oncology, St-Petersburg Medical Academy, St-Petersburg/RU
  • 7Oncology, Box Hill Hospital, West Midlands/UK
  • 8Research And Development, Sanofi, Vitry-sur-Seine/FR
  • 9Oncology, Box Hill Hospital, Victoria/AU
  • 10Oncology, University of Florida, Gainesville/US

Abstract

Background

The VELOUR study [NCT00561470] in previously treated mCRC showed significant improvement in overall survival (13.5 vs 12.06 months; P = 0.0032) and PFS (6.9 vs 4.67 months; P = 0.00007) with aflibercept-FOLFIRI vs placebo-FOLFIRI. Two sensitivity analyses (SAs) were performed to assess robustness of PFS observed in the primary analysis.

Methods

In the primary PFS analysis, an Independent Review Committee (IRC) assessed disease progression per radiological tumor progression. The primary PFS analysis was performed at a conservative α level of 0.0001. In SA #1, patients with documented radiological progression or death occurring >9 weeks after the last valid tumor assessment without progression and patients who received further anti-cancer therapy without documented progression were censored at the last valid tumor assessment date. In SA #2, PFS was per the investigators' assessment of lesions; clinical progression was considered as an event.

Results

SA #1 (Table) showed significant improvement in PFS with aflibercept-FOLFIRI compared to placebo-FOLFIRI (P < 0.00001), thus confirming primary PFS analysis. SA #2 also showed an improvement in PFS with aflibercept vs placebo; difference was not significant (P = 0.0017) at the 0.0001 α level. Discrepancies between IRC and investigators' assessments were noted in placebo (n = 273, 45.8%) and aflibercept (n = 231, 39.3%) arms. An unstratified log-rank test comparing primary PFS in the two arms was consistent with the stratified analysis, showing a significant difference in PFS with aflibercept (P = 0.00005). Aflibercept showed typical anti-VEGF side effects.

Conclusion

The data from these PFS sensitivity analyses (SAs) are consistent with the primary analysis of PFS in VELOUR, further supporting the statistically significant and clinically meaningful improvement in PFS seen in the primary analysis. Funded by Sanofi & Regeneron

Analysis: PFS (months) Placebo N = 614 Aflibercept N = 612 HR [99.99% CI]
Primary: 4.67 4.07 – 5.55 6.90 5.88 – 7.85 0.758 [0.578 – 0.995]
SA #1: 4.53 4.07 – 5.68 6.97 6.05 – 8.51 0.654 [0.477 – 0.895]
SA #2: 4.50 4.04 – 5.55 6.24 5.49 – 7.19 0.814 [0.630 – 1.052]
Disclosure

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

J. Tabernero: I have an advisory relationship with sanofi, for which I have been compensated.

R. Lakomy: I have received research funding from Sanofi.

P. Ruff: I have received honorarium from Amgen, Merck AG, Roche, Sanofi and Pfizer. I have received research funding from Amgen, Merck AG, Sanofi and Pfizer. I have received travel grants from Amgen, Roche, and Pfizer.

D. Ferry: I have an advisory relationship with Sanofi. I have received honorarium from Sanofi.

E. Boelle: I am an employee of Sanofi.

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

All other authors have declared no conflicts of interest.