DOSING OF BEVACIZUMAB IN COLORECTAL CANCER

Ann Oncol. 2015 Apr 23. pii: mdv197. [Epub ahead of print]

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.

Iwamoto S1, Takahashi T2, Tamagawa H3, Nakamura M4, Munemoto Y5, Kato T6, Hata T7, Denda T8, Morita Y9, Inukai M10, Kunieda K11, Nagata N12, Kurachi K13, Ina K14, Ooshiro M15, Shimoyama T16, Baba H17, Oba K18, Sakamoto J19, Mishima H20.

Author information

Abstract

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.