Predictive factors for early progression during induction chemotherapy and chemotherapy-free interval: analysis from PRODIGE 9 trial

Thomas Aparicio, Jaafar Bennouna, Karine Le Malicot, Valérie Boige, Julien Taieb, Olivier Bouché, Jean-Marc Phelip, Eric François, Christian Borel, Roger Faroux, Laetitia Dahan, Jean-Baptiste Bachet, Joelle Egreteau, Marie-Christine Kaminsky, Jean-Marc Gornet, Oana Cojocarasu, Mohamed Gasmi, Véronique Guerin-Meyer, Côme Lepage, François Ghiringhelli, for PRODIGE investigators/collaborators, Thomas Aparicio, Jaafar Bennouna, Karine Le Malicot, Valérie Boige, Julien Taieb, Olivier Bouché, Jean-Marc Phelip, Eric François, Christian Borel, Roger Faroux, Laetitia Dahan, Jean-Baptiste Bachet, Joelle Egreteau, Marie-Christine Kaminsky, Jean-Marc Gornet, Oana Cojocarasu, Mohamed Gasmi, Véronique Guerin-Meyer, Côme Lepage, François Ghiringhelli, for PRODIGE investigators/collaborators

Abstract

Background: Identifying patients with metastatic colorectal cancer who will have an early disease progression during induction chemotherapy (IC) and identifying patients who may have a chemotherapy-free interval (CFI) after IC are two major challenges.

Methods: A logistic model was used to identify factors associated with early progression during IC and with short duration of the first CFI in 488 patients enrolled in the PRODIGE 9 trial. Independent factors were defined with a threshold 0.10.

Results: In multivariate analysis, baseline leukocytes >10 × 109/L (OR = 1.98 [1.02-3.8], p = 0.04), and stable or increasing CEA at 2 months (OR = 3.61 [1.68-7.75], p = 0.01) were independent factors associated with progression during IC. Male gender (OR = 1.725 [0.92-3.325], p = 0.09) and no tumour response at first evaluation (OR = 1.90 [0.96-3.76], p = 0.07) were significantly associated with a short CFI. The presence of BRAF V600E mutation was also associated with short CFI (OR = 4.59 [0.95; 22.3], p = 0.058).

Conclusion: High baseline leukocyte count and the lack of CEA decrease level at first evaluation were associated with early progression, and could be in favour of early chemotherapy intensification. Male gender, no tumour response at first evaluation and BRAF mutation are associated with a short CFI, and may be considered for maintenance chemotherapy after IC.

Clinical trial number: NCT00952029.

Conflict of interest statement

Pr Aparicio reports personal grants; consultancy for BMS: payments for development of educational presentations for Ipsen Pharma Roche, Servier, Amgen; travel grants from Ipsen Pharma, Roche, Bayer. Pr Ghiringhelli reports personal grants consultancy for Roche, AstraZeneca; payments for development of educational presentations for Roche, Servier, Amgen, Merck; MSD: travel grants from Amgen, Servier, Roche. Pr Bouché reports personal grants consultancy for Roche, Merck, Amgen; payments for development of educational presentations for Bayer, Pierre Fabre, Servier, Amgen; travel grants from Lilly, Roche, Bayer. Pr Bachet reports personal grants consultancy for Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre and Servier; payments for development of educational presentations for Amgen, AstraZeneca, Bayer, Merck Serono, Mundipharma, Pierre Fabre, Roche, Sanofi and Servier; travel grants from Amgen, Bayer, Merck Serono, Roche, Sanofi and Servier. Dr. Cojocarasu reports payment for board participation from Sanofi; travel grants from Amgen, Roche and Pfizer. Dr. Boige reports grants, personal fees and non-financial support from Merck Serono, Bayer, Amgen, Sanofi, Daiichi Sankyo, Novartis, Roche and Prestizia, outside the submitted work. Pr Taieb reports personal grants for consultancy for Abbvie, Amgen, Baxalta, Celgene, Lilly, Merck and Roche; payment for lectures including service on speaker’s bureau for ABBVIE, Amgen, Celgene, Lilly, Merck and Roche; payments for development of educational presentations for Roche and travel grants from Roche and Merck. Pr Phelip reports personal grants for board membership for Roche, Sanofi, Lilly Merck and Amgen; consultancy for Lilly and Roche; payments for development of educational presentations for Roche, Sanofi, Lilly Merck and Amgen. Pr Phelip reports grants for his institution for board membership for Roche and Merck; payments of grants from Merck and Roche. Dr. François reports personal grants for board membership for Roche, Merck and Sanofi. Dr. Faroux reports personal grants for clinical research for Merck; payment for lectures and consultancy for Amgen, Merck and Roche; travel grants from Amgen, Celgene, Merck and Roche. Pr Lepage reports personal grants for board membership for AAA, grants from Novartis and travel grants from Ipsen pharma, Amgen and Bayer. Dr. Bennouna reports personal grants for board membership for Roche, Boehringer-Ingelheim, AstraZeneca, Servier and BMS; payment for lectures including service on speaker’s bureau for Roche and AstraZeneca, and travel grants from Roche and BMS. Pr Dahan reports personal grants for clinical research for Ipsen, Lilly, MSD and Sanofi; for payment for lectures and consultancy for Amgen, Baxalta, Celgene, Lilly, Merck, Sanofi and Roche; travel grants from Celgene, Ipsen and Sanofi. No other disclosures are reported.

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