P-0226 - Evaluation of the Effect of Aflibercept (Z) on OS by Timing of 1st Line Disease Progression: A Post-hoc Analysis of the VELOUR Trial

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Edith Mitchell
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors E. Mitchell1, R. Vishwanath2, P. Hoff3, G. van Hazel4, D. Cunningham5, D. Arnold6, H. Schmoll7, A. ten Tije8, J. Mckendrick9, F. Joulain10, M. Andria11
  • 1Kimmel Cancer Center at Jefferson, Philadelphia/US
  • 2Sanofi Oncology, Cambridge/US
  • 3Centro de Oncologia, Hospital Sírio Libanês, São Paulo, Brazil, /
  • 4University of Western Australia, Perth/AU
  • 5Royal Marsden Hospital, Sutton/UK
  • 6Tumor Biology Center, Freiburg/DE
  • 7Martin Luther University Halle-Wittenberg, Halle/DE
  • 8Amphia Hospital Breda, Breda/NL
  • 9Box Hill Hospital, Box Hill/AU
  • 10Sanofi, Chilly Mazarin/FR
  • 11Regeneron Pharmaceuticals Inc., Tarrytown/US



An overall survival (OS) of 20.6 months (95% CI, 17.7 to 24.6) and median progression free survival (PFS) of 8.0 months (P = 0.26) were previously demonstrated with first-line (1L) FOLFOX6 followed by FOLFIRI (F) (Tournigand, JCO 2004). Treatment of metastatic colorectal cancer (mCRC) patients with 1L combination chemotherapy (CT) and bevacizumab (B) results in a significant increase in median PFS (9.4 mos) (HR, 0.83; 97.5% CI, 0.72 to 0.95; P = 0.0023) compared to CT alone (8.0 mos) (Saltz, JCO 2008). The heterogeneity in the timing of progression in 1L therapy could potentially impact the benefit of 2nd-line treatments. The VELOUR trial (NCT00561470) demonstrated that angiogenesis inhibition with the addition of aflibercept (Z) (known as ziv-aflibercept in the US) to the combination of 5-fluouracil, leucovorin, and irinotecan (FOLFIRI) after progression on oxaliplatin-based CT. The consistency of the treatment effect of Z + FOLFIRI (F) vs placebo (P) + F was evaluated based on time to progression after 1st line therapy.


The VELOUR ITT population (excluding pts who relapsed during or within 6 months of completing oxaliplatin-based adjuvant therapy (rapid adjuvant progressors)) (N = 1102) was analyzed based on time by the timeframe of 1st line progression (PFS < 3 months, 3-6 months, 6-9 months or ≥ 9 months) in a post-hoc analysis.


Z had an overall survival (OS) benefit in pts across all subgroups analyzed irrespective of the timing of 1st line PFS. A similar benefit was observed with PFS.


In this post hoc analysis, the addition of Z to 2nd line F was beneficial regardless of the timing of progression during 1st line treatment. These results emphasize the consistent benefits of Z in combination with F in mCRC patients who failed an oxaliplatin-based regimen whether the duration of disease control with 1L regimen was short or of longer term. Research supported by Sanofi, in collaboration with Regeneron Pharmaceuticals.

No medical writing support utilized.