528P - Aflibercept + FOLFIRI for treatment of metastatic colorectal cancer after oxaliplatin failure: 4th interim safety data from the global aflibercept...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter Luca Frassineti
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors L. Frassineti1, M. Di Bartolomeo2, V. Heinemann3, A.L. Thomas4, J. Taieb5, G. Lledo6, Y. Moore7, C. Zilocchi8, S. Brette9, A. Sobrero10, R. Bordonaro11
  • 1Medical Oncology, IRCCS - IRST (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori), 47014 - Meldola FC/IT
  • 2Oncologia Medica 1, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milano/IT
  • 3Department Of Medical Oncology And Comprehensive Cancer Center, Ludwig-Maximilian-University of Munich, Munich/DE
  • 4Cancer Studies And Molecular Medicine, University of Leicester, Leicester/GB
  • 5Gi Oncology, APHP and Paris Descartes University, Paris/FR
  • 6Gastroenterology, Hôpital privé Jean Mermoz, LYON/FR
  • 7Oncology Gma, Sanofi, Cambridge/US
  • 8Medical Oncology, Sanofi, Milan/IT
  • 9Clinical Sciences And Operations – Biostatistics For Gma, Lincoln, Boulogne/FR
  • 10Oncologia Medica, IRCCS San Martino, Genova/IT
  • 11Medical Oncology, ARNAS Garibaldi Catania, Catania/IT



In VELOUR, aflibercept (ziv-aflibercept in the US) + FOLFIRI demonstrated a statistically significant improvement in overall survival vs placebo + FOLFIRI in metastatic colorectal cancer (mCRC) patients (pts) previously treated with an oxaliplatin-containing regimen. Results supported initiation of the global Aflibercept Safety and Quality-of-Life (QoL) Program composed of 2 clinical studies (ASQoP; AFEQT) to capture utility values from QoL instruments and collect safety data from a population similar to that in VELOUR in a real-life setting. We report safety data from the 4th interim analysis of these ongoing studies.


ASQoP and AFEQT are single-arm, open-label trials in mCRC pts previously treated with an oxaliplatin-containing regimen. Eligible pts received aflibercept 4 mg/kg every 2 weeks on day 1 of each cycle followed by FOLFIRI. FOLFIRI starting dose and subsequent additional dose modifications are at discretion of the treating physician.


At data cut-off for this interim analysis, the safety population (n = 688) was compared with VELOUR. In 44% of ASQoP vs 33.5% of VELOUR, pts were ≥65 years; 10.8% of ASQoP vs 5.4% of VELOUR were ≥75 years. ASQoP pts received a median of 6 treatment cycles while VELOUR pts received a median of 9. Grade (G) 3/4 adverse events (AEs) were experienced by 72.2% of ASQoP pts vs 83.5% in VELOUR. Most were G3. G4 hypertension or diarrhea was not reported. Table shows selected G3/4 AEs.

Adverse Events, % Aflibercept + FOLFIRI (n = 688) Aflibercept + FOLFIRI (n = 611)
Grade 3/4 (%) Grade 3/4 (%)
Proteinuria 3.6 7.9
Stomatitis and ulceration (high level term) 9.6 13.8
Diarrhea (preferred term) 14.1 19.3
Infections and infestations (system organ class) 9.6 12.3
Hypertension 23.0 19.3
Arterial thromboembolic event 0.6 1.8
Venous thromboembolic event 4.4 7.9
Fistula (gastrointestinal [GI] origin) 0.6 0.3
GI perforation 1.3 0.5


Interim safety analysis from ASQoP/AFEQT has identified no new safety signals. Despite a greater % of elderly pts in ASQoP/AFEQT, reported incidence of toxicity is generally similar or less than VELOUR. Differences in AE incidence in ASQoP/AFEQT vs VELOUR may be related to the VELOUR protocol requirement of full-dose FOLFIRI initiation and current overall exposure differences.


J. Taieb: has conflicts of interest related to advisory boards for Sanofi and for corporate-sponsored research for Sanofi; Y. Moore: formerly held a leadership position at Sanofi at the time this study was conducted and has stock ownership in Sanofi; C. Zilocchi: is an employee of Sanofi and has stock ownership; S. Brette: is an employee (biostatistician) of Lincoln, which is a consultant for Sanofi. A. Sobrero: has received honoraria for participating in advisory boards for Bayer, Roche, Sanofi, Celgene, Merck, and Amgen. All other authors have declared no conflicts of interest.