Résumé
Rationnel
Une association fluoropyrimidine plus irinotécan ou oxaliplatine, avec bévacizumab (un anticorps monoclonal dirigé contre le vascular endothelial growth factor), est le traitement de référence de première-ligne du cancer colorectal. Avant l’introduction du bévacizumab, la chimiothérapie avec l’association 5-fluorouracile, leucovorine, oxaliplatine, et irinotecan (FOLFOXIRI) a montré une efficacité supérieure comparée à l’association 5-fluorouracile, leucovorine, et irinotecan (FOLFIRI). Dans une étude de phase 2, le FOLFOXIRI plus bévacizumab a montré une efficacité prometteuse et un taux d’effets secondaires acceptable.
Méthodes
Cinq cent-huit patients atteints d’un cancer colorectal métastatique non opérable ont été randomisés entre un traitement par FOLFIRI plus bévacizumab (groupe témoin) ou FOLFOXIRI plus bévacizumab (groupe expérimental). Jusqu’à 12 cycles de chimiothérapie ont été administrés, suivis de 5-fluorouracile plus bévacizumab jusqu’à progression tumorale. Le critère de jugement principal était la survie sans progression.
Résultats
La survie sans progression médiane était de 12,1 mois dans le bras expérimental, comparée à 9,7 mois dans le bras témoin (hazard ratio pour la progression: 0,75; IC 95%: 0,62-0,90; p=0,003). Le taux de réponses objectives était de 65% dans le bras expérimental et 53% dans le bras témoin (p=0,006). La survie globale était non significativement allongée dans le bras expérimental (31,0 vs 25,8 mois; hazard ratio pour le décès, 0,79; IC 95%: 0,63-1,00; p=0,054). L’incidence des toxicités de grade 3 ou 4, neurologique, stomatites, diarrhée et neutropénie était significativement plus élevée dans le bras expérimental. Conclusion: La chimiothérapie par FOLFOXIRI plus bevacizumab, comparée au FOLFIRI plus bévacizumab, améliore le pronostic des patients atteints d’un cancer colorectal métastatique et augmente l’incidence de certains effets indésirables.
Abstract
Abstract
A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard first-line treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects.
Methods
We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival.
Results
The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62 to 0.90; P = 0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P = 0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63 to 1.00; P = 0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group.
Conclusions
FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. (Funded by the Gruppo Oncologico Nord Ovest and others; ClinicalTrials.gov number, NCT00719797.)
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Références
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Venook AP, Niedzwiecki D, Lenz HJ, et al (2014) CALGB/ SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin with bevacizumab or cetuximab for patients with KRAS wild-type untreated metastatic adenocarcinoma of the colon or rectum. J Clin Oncol 32:5s (suppl abstr LBA3)
Cremolini C, Loupakis F, Masi G, et al (2015) FOLFOXIRI plus bevacizumab vs FOLFIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: Updated survival results of the phase III TRIBE trial by the GONO group. J Clin Oncol 33 (suppl 3; abstr 657)
Falcone A, Ricci S, Brunetti I, et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25:1670–6
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Aparicio, T. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer F. Loupakis (2014) N Engl J Med 371: 17. Colon Rectum 9, 111–113 (2015). https://doi.org/10.1007/s11725-015-0581-7
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DOI: https://doi.org/10.1007/s11725-015-0581-7