P-0288 - Aflibercept/FOLFIRI vs Placebo/FOLFIRI in Metastatic Colorectal Cancer: A Post-Hoc Analysis of Median Overall Survival in VELOUR From the Retrospect...

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter Josep Tabernero
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors J. Tabernero1, T. Macarulla1, Y. Humblet2, H. Kroening3, C. Grávalos4, S. Le-Guennec4, E. Dochy5
  • 1Vall d'Hebron University Hospital, Barcelona/ES
  • 2St-Luc University Hospital, Brussels/BE
  • 3Schwerpunktpraxis für Hämatologie und Onkologie, Magdeburg/DE
  • 4Sanofi, Vitry sur Seine/FR
  • 5Sanofi, Diegem/BE



Treatment of patients with metastatic colorectal cancer (mCRC) with first-line (1L) FOLFOX6 followed by FOLFIRI has demonstrated 20.6 months (95% confidence interval [CI]: 17.7-24.6) median overall survival (OS) (Tournigand C et al. J Clin Oncol. 2004;22(2):229-237). Treatment with 1L chemotherapy (CT) + bevacizumab (Bev) followed by second-line CT +/- Bev in the ML18147 Trial, increased median OS to 23.9 months (95% CI: 22-25.7) with CT + Bev versus 22.5 months (95% CI: 21.4-24.5) with CT alone (hazard ratio [HR] = 0.90; 95% CI: 0.77-1.05) from the start of 1L treatment (Bennouna J et al. Lancet Oncol. 2013;14(1):29-37). In the ITT population of the VELOUR trial (NCT00561470), in mCRC patients previously treated with oxaliplatin, addition of aflibercept (Afl; ziv-aflibercept in the United States) to FOLFIRI increased median OS to 13.5 months versus 12.06 months in the FOLFIRI + placebo arm (∆ OS, 1.4 months; HR = 0.817; 95.34% CI: 0.713-0.937; P < 0.0032). In VELOUR, ∼10% of enrolled patients were adjuvant rapid relapsers (ARR), defined as experiencing recurrence during or within 6 months of completing oxaliplatin-based adjuvant therapy. A post-hoc analysis of patients who enrolled in VELOUR after receiving 1L therapy (ie, ITT population subsequent to exclusion of ARR) increased median OS to 13.8 months in the Afl + FOLFIRI arm versus 11.9 months for FOLFIRI + placebo (∆OS, 1.9 months; adjusted HR = 0.80; 95% CI: 0.69-0.92 [Joulain F et al. Ann Oncol. 2012;23(suppl 9):ix214. Poster 633P]). We performed an additional post-hoc analysis of VELOUR data to evaluate survival from start of 1L treatment until death in the ITT minus ARR population, according to prior Bev treatment.


Data from VELOUR were analyzed by the Kaplan-Meier method to determine median OS from first day of 1L treatment until death in prespecified subgroups according to prior Bev exposure. Probability of survival at 48 months from 1L treatment in each subgroup was also determined. The population in this analysis was the VELOUR ITT (n = 1226), excluding ARR (n = 124) (who enrolled directly into VELOUR as described previously (Van Cutsem E et al. Eur J Cancer. 2013;49(suppl 2):Abstract 2260); it also excluded 1 patient (Afl) with incomplete start date of 1L therapy, yielding n = 1101 (ie, 1226 − 124 − 1).


Addition of Afl to FOLFIRI resulted in median OS improvement of >3 months for mCRC patients treated in 1L with an oxaliplatin-based regimen, with a median OS of >2 years (Table 1). The probability of survival at 48 months following FOLFIRI-Afl treatment was ∼20% in all patient subgroups analyzed (Table 2).


In this post-hoc analysis of the VELOUR trial, overall duration of survival from initiation of first-line treatment is >2 years. Aflibercept is active in the second-line with a numerical difference of >3 months in median overall survival from first day of first-line therapy. The probability of survival at 48 months is approximately 20% in all patients regardless of the use of prior bevacizumab. However, the survival estimates at 48 months need to be interpreted with caution due to the limited number of patients.