Some patients (pts) with mCRC have an early progression during induction chemotherapy (IC). Early identification of these pts is an important challenge in order to intensified front line treatment. For pts who have a tumor response or stabilization after IC a chemotherapy-free interval (CFI) could be proposed. Identification of the subgroup of pts that should not stopped chemotherapy (CT) and pts that will benefit from a long CFI is also of importance.
PRODIGE 9 pts had 12 courses of FOLFIRI + bevacizumab before an IC with or without bevacizumab monotherapy. As the pts are randomized before IC the whole strategy could be assessed. Following factors were evaluated for early progression during IC and for early (< 3 mths) or late progression (≥ 5 mths) during 1st CFI: treatment arm, sex, age, WHO PS, primary tumor resected, number of metastatic site, primary localization, leucocyte, platelets, alkaline phosphatase, CEA level, KRAS mutation, BRAF mutation and decrease of CEA at 2 months. Tumor response at the end of IC and early shrinkage at 1st evaluation were evaluated only for CFI duration. A logistic model was used to identify the prognostic factors with a . A significance level of 0.2 was required to enter into the model and to stay in the model.
An early progression during IC occurred in 85 pts. Leucocytes >10 x109/L (p = 0.02), and decrease of less than 50% of CEA at 2 mths (p = 0.01) were associated with early progression. A first CFI was done in 344 pts. 128 pts had a short CFI, 100 an intermediate one between 3 and 5 mths and 116 a long CFI. Two factors were significantly associated with a short CFI: normal CEA at baseline (p = 0.03) and complete or partial response at 1st evaluation (p = 0.08). In the sub-group of 95 pts with BRAF determination, these 2 results were the same.
High baseline leucocytes count and the lack of decrease of CEA at 1st evaluation are associated with early progression and could be considered in favor of an early CT intensification. Two factors predict significantly CFI duration: Baseline CEA and tumor response to 1st evaluation. Surprisingly, our results suggest that a high baseline CEA and a stable disease at 1st evaluation are associated with a longer CFI.
Clinical trial identification
EUDRACT n°2011-002974-22 NCT00952029
Legal entity responsible for the study
T. Aparicio: Personal grant and consultancy for Pierre Fabre, grants from Roche and Amgen, payments for development of educational presentations for Novartis Oncology, Pfizer, Sanofi, Roche, travel grants from Ipsen Pharma, Novartis Oncology, Sanofi, Roche. J. Bennouna: Personal grants for board membership for Roche, Boehringer-Ingelheim, Astra-Zeneca, Servier and BMS, payment for lectures including service on speakers’ bureau for Roche, Astra-Zeneca and travel grants from Roche and BMS. V. Boige: Grants, personal fees and non-financial support from Merck Serono, Bayer, Amgen, Sanofi, Daiichi Sankyo, Novartis, Roche, Prestizia outside the submitted work. J. Taieb: Personal grants for consultancy for Abbvie, Amgen, Baxalta, Celgene, Lilly, Merck, Roche, payment for lectures for ABBVIE, Amgen, Celgene, Lilly, Merck, Roche, educational presentations for Roche and travel grants from Roche and Merck. O. Bouche: Personal grants for consultancy for Roche, Merck, Amgen and Bayer, payment for lectures including service on speakers’ bureau for Novartis, payments for development of educational presentations for Lilly. E. Francois: Personal grants for board membership for Roche, Merck and Sanofi. J-M. Phelip: Grants for board membership for Roche, Sanofi, Lilly Merck and Amgen, consultancy for Lilly and Roche, educational presentations for Roche, Sanofi, Lilly Merck and Amgen, grants for institution for board membership for Roche and Merck. L. Dahan: Grants from Ipsen Pharma, Lilly, Msd, Sanofi, Amgen, Celgene, Merck, Roche, Baxalta. J-B. Bachet: Fees from Amgen, Bayer, Celgène, Merck Serono, Sanofi, consultant for Amgen, Bayer, Merck Serono, Servier. J-M. Gornet: Grants from Roche, Amgen, Lilly, Merck, Novartis, Abbvie, Mayoly Spindler, MSD. F. Ghiringhelli: Grants from Amgen and Merck. C. Lepage: Personal grants for board membership for AAA, grants from Novartis and travel grants from Ipsen pharma, Amgen and Bayer. All other authors have declared no conflicts of interest.