FOLFOXIRI reintroduction in metastatic colorectal cancer
Mené en Italie sur 679 patients atteints d'un cancer colorectal de stade métastatique (âge : 18-75 ans), cet essai de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de deux stratégies thérapeutiques, l'une consistant en un traitement de première ligne de type FOLFOXIRI combiné au bévacizumab et réintroduit à l'identique après la progression de la maladie, et l'autre consistant en l'administration séquentielle d'une chimiothérapie de première ligne de type mFOLFOX6 et d'un traitement de type FOLFIRI avec le bévacizumab
FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) is an effective first-line combination therapy for metastatic colorectal cancer that offers better outcomes in terms of overall response rate, progression-free survival, and overall survival compared with standard doublet chemotherapy. However, this improvement comes at the price of more toxicity. The TRIBE trial showed that FOLFOXIRI plus bevacizumab significantly improved progression-free survival compared with FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. Longer median overall survival was reported in patients with RAS and BRAF wild-type cancers compared with mutated cancers, but the treatment effect from the strategy itself was not significantly different between the molecular subgroups. These results suggest that if the TRIBE strategy is adopted the baseline RAS and BRAF-mutational status does not need to be considered. However, the role of additional targeted drugs combined with FOLFOXIRI remains uncertain—particularly anti-EGFR drugs. There are ongoing phase 3 trials of modified FOLFOXIRI plus panitumumab regimen versus mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) plus panitumumab in patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer.
The Lancet Oncology , commentaire, 2019