604TiP - PRODIGE 25 (FFCD 11-01) - Phase II randomized trial evaluating aflibercept associated with LV5FU2 regimen as first line treatment of non-resectable...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Colon Cancer
Rectal Cancer
Presenter Jean Louis Legoux
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors J.L. Legoux1, K. Le Malicot2, R. Faroux3, V. Boige4, N. Barriere5, J. Egreteau6, Y. Rinaldi7, E. Maillard8, M. Baconnier9, C. Lecaille10, S. Herrmann-Gandara1, A. Vimal11, Y. Touchefeu12, J. Raimbourg13, T. Aparicio14
  • 1Hepato-gatroenterology And Digestive Oncology, C.H.R. Orleans - La Source, 45100 - Orleans/FR
  • 2Biostatistics, Fédération Francophone de Cancérologie Digestive (FFCD), 21079 - Dijon/FR
  • 3Service D'hge, CHD Vendee - Hopital Les Oudairies, 85925 - La Roche sur Yon/FR
  • 4Digestive Oncology, Institut Gustave Roussy, Villejuif/FR
  • 5Hepato-gatroenterology And Digestive Oncology, Hôpital Européen, Marseille/FR
  • 6Medical Oncology, CH Sud Bretagne, Lorient/FR
  • 7Service D'hge, Hôpital européen, Marseille/FR
  • 8Hepato-gastroenterology, CH d'Annecy, Annecy/FR
  • 9Hepato-gatroenterology And Digestive Oncology, CH d'Annecy, Annecy/FR
  • 10Hepato-gatroenterology And Digestive Oncology, Polyclinique Bordeaux Nord Aquitaine, Bordeaux/FR
  • 11Medical Oncology, CHU Estaing, Clermont-Ferrand/FR
  • 12Hepato-gastroenterology, CHU de Nantes, 44000 - Nantes/FR
  • 13Medical Oncology, Institut de Cancérologie de l’Ouest, Nantes/FR
  • 14Gastroenterology, Hôpital Avicenne, 93000 - Bobigny/FR

Abstract

Background

Aflibercept has already been used in combination with FOLFIRI in the VELOUR trial (1). The aflibercept-LV5FU2 combination can be useful and well tolerated in patients (pts) with never resectable/non symptomatic metastatic colorectal cancer, for whom 5-FU monotherapy can be suggested to delay the toxicities of combined chemotherapies, then eligible for sequential treatment with first-line 5-FU monotherapy. Within this context, it is possible for aflibercept to provide a survival benefit. VELOUR trial did not indicate that toxicity would have a major effect on quality of life and increase the hope of prolonged progression-free survival in the arm with aflibercept. A previous pharmacogenetic analysis of the FFCD 2000-05 phase III trial (2) showed a prognostic and predictive effect of the thymidylate synthase (TS)-5'UTR polymorphism for response and PFS: the 5-FU monotherapy efficacy was increased in TS 5'3R/3R pts vs 2R2R-2R3R (2). Stratification in this criterion will confirm or not the prognostic or predictive value of these polymorphisms if linked to the 5-FU efficacy.

Trial design

The major eligibility criteria are: age ≥ 65, performance status WHO ≤ 2, central genotyping of TS in blood DNA. Treatment is administered every14 days with simplified LV5FU2 regimen, preceded or not by perfusion of 4 mg/kg aflibercept. The treatment will be stopped in case of progression (evaluation each 8 weeks) or inacceptable toxicity. The main judgement criterion is proportion of pts alive and without radiologic progression within 6 months. A proportion of more than 40% pts will be interesting and a rate of 60% is expected (α = 5%, Binomial-exact method and a power of 90%). Secondary criteria are: tolerance of the LV5FU2-aflibercept combination, time to final deterioration in quality of life, overall survival, prognostic value of TS-5'UTR polymorphism on PFS. Stratification factors are: centre, age:  75, TS-5'UTR polymorphism, metastatic site (1 vs >1). Status: 18 of planned 118 patients have been randomized. References: (1) Van Cutsem E et al: J Clin Oncol 30:3499-506, 2012 (2), Boige V et al: J Clin Oncol 28:2556-64, 2010

Clinical trial identification

EudraCT 2014-001837-10; 05 September 2014

Legal entity responsible for the study

FFCD

Funding

Sanofi

Disclosure

All authors have declared no conflicts of interest.