FOLFIRI plus bevacizumab as second-line therapy in patients with metastatic colorectal cancer after first-line bevacizumab plus oxaliplatin-based therapy: the randomized phase III EAGLE study
Mené au Japon sur 387 patients atteints d'un cancer colorectal métastatique, cet essai randomisé multicentrique de phase III compare l'efficacité, du point de vue de la survie sans progression, et la toxicité de deux doses de bévacizumab en combinaison avec une chimiothérapie FOLFIRI pour un traitement de deuxième ligne
Background : A targeted agent combined with chemotherapy is the standard treatment in patients with metastatic colorectal cancer (mCRC). The present phase III study was conducted to compare two doses of bevacizumab combined with irinotecan, 5-fluorouracil/leucovorin (FOLFIRI) in the second-line setting after first-line therapy with bevacizumab plus oxaliplatin-based therapy. Patient and Methods : Patients were randomized to receive FOLFIRI plus bevacizumab 5 mg/kg or 10 mg/kg in 2-week cycles until disease progression. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS), time to treatment failure (TTF), and safety. Results : 387 patients were randomized between September 2009 and January 2012 from 100 institutions in Japan. Baseline patient characteristics were well balanced between the two groups. Efficacy was evaluated in 369 patients (5 mg/kg, n=181; 10 mg/kg, n=188). Safety was evaluated in 365 patients (5 mg/kg, n=180; 10 mg/kg, n=185). The median PFS was 6.1 months vs. 6.4 months (hazard ratio, 0.95; 95% CI, 0.75–1.21; p=0.676), and median TTF was 5.2 months vs. 5.2 months (hazard ratio, 1.01; 95% CI, 0.81–1.25; p=0.967), respectively, for the bevacizumab 5 mg/kg and 10 mg/kg groups. Follow-up of OS is currently ongoing. Adverse events, including hypertension and hemorrhage, occurred at similar rates in both groups. Conclusion : Bevacizumab 10 mg/kg plus FOLFIRI as second-line treatment did not prolong PFS compared with bevacizumab 5 mg/kg plus FOLFIRI in patients with mCRC. If bevacizumab is continued after first-line therapy in mCRC, a dose of 5 mg/kg is appropriate for use as second-line treatment. Clinical trial identifier : UMIN000002557.
Annals of Oncology 2015