506PD - Interim analysis of PRODIGE 9, a randomized phase III trial comparing no treatment to bevacizumab maintenance during chemotherapy-free intervals in...

Date 27 September 2014
Event ESMO 2014
Session Gastrointestinal tumours, colorectal
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter Thomas Aparicio
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors T. Aparicio1, J. Bennouna2, K. Le Malicot3, F. Ghiringhelli4, V. Boige5, J. Taieb6, O. Bouché7, E. Francois8, J. Phelip9, F. Borel10, R. Faroux11, J. Seitz12, S. Jacquot13, D. Genet14, C. Lepage15
  • 1Gastroenterology And Digestive Oncology, Hôpital Avicenne, 93000 - Bobigny/FR
  • 2Department Of Medical Oncology, Institut de Cancérologie de l'Ouest, 44805 - Saint-Herblain cedex/FR
  • 3Biostatistic, FFCD, Dijon/FR
  • 4Oncology, CLCC GF Leclerc, Dijon/FR
  • 5Oncologic Medicine, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 6Gastroenterology And Digestive Oncology, Hopital Européen Georges Pompidou, 75015 - Paris/FR
  • 7Gastroenterology And Digestive Oncology, Hopital Robert Debré, Reims/FR
  • 8Medical Oncology, Antoine Lacassagne Cancer Institute, Nice/FR
  • 9Gastro-entérologie Et Hépatologie, CHU de Saint Etienne, Saint Etienne/FR
  • 10Medical Oncology, Centre Paul Strauss, Strasbourg/FR
  • 11Gastroenterology And Digestive Oncology, CHD Vendee - Hopital Les Oudairies, La Roche sur Yon/FR
  • 12Oncologie Digestive, Hôpital de La Timone, Marseille/FR
  • 13Oncology, Clinique - Oncologie Radiothérapie, Montpellier/FR
  • 14Oncology, chu de limoges, limoges/FR
  • 15Hepatogastroenterology Department, University Hospital, 21079 - DIJON Cedex/FR




The FOLFIRI + bevacizumab (bev) regimen is a standard 1st-line chemotherapy (CT) in metastatic colorectal cancer (mCRC). Several trials have evaluated chemotherapy-free intervals (CFI) with the aim of prevening patients (pts) from experiencing toxicities, with conflicting results.


This study aimed to compare the tumour control duration (TCD) by a 1st-line CT followed by either bev maintenance (Arm A) or no treatment during CFI (Arm B). Both arms start with 12 cycles of induction CT of FOLFIRI + bev; then a CFI is made until progression. CT is reintroduced at progression, for a 8 further cycles; then a new CFI is put in place and so on. The TCD is defined by the time between randomization and strategy failure corresponding to tumour progression during a FOLFIRI + bev sequence. It was expected that bev maintenance will extend TCD from 10 to 14 months. We present the results of the planned interim analysis (IA) after 203 events were observed.


494 pts were enrolled from March 2010 to July 2013. The IA was performed on the data of 490 pts (245 in both arms). The median age was 64.5 years; 218 (44%) pts had a non-resected primary tumour. During induction CT, 68% of the pts received the 12 planned cycles. At the time of analysis, 60% of the pts received only the 1st sequence of FOLFIRI + bev, and 29% received 2 sequences. The median TCD was 14.3 months in arm A and 13.4 months in arm B (HR = 0.98, p = 0.86). The estimated progression free survival (PFS) was 9.2 months [8.2; 9.7] in arm A and 8.0 months [7.7; 9.0] in arm B. The median overall survival was not met. Grade 3-4 toxicities were observed in 74% of the pts in arm A and 71% in arm B. No safety issue was detected based on the serious adverse events (SAE).


The strategy evaluated in PRODIGE 9, to alternate CT sequences with or without bev maintenance during CFI, revealed an impressive TCD in both groups and longer than expected in arm B. The IA shows no significant improvement of TCD with bev maintenance therapy. A trend to a PFS improvement is observed in the bev maintenance arm that should be confirmed by the final analysis planned in 2015. No increase in toxicity was observed in the bev maintenance arm. This study validates the concept of a chemo re-introduction strategy with irinotecan-based regimen in first-line mCRC.


T. Aparicio: Roche, Sanofi, Merck, Novartis; J. Bennouna: Roche; J. Taieb: Roche; O. Bouché: Roche; J. Phelip: Roche. All other authors have declared no conflicts of interest.