Cetuximab is less effective immediately after bevacizumab in RAS wild type patients with metastatic colorectal cancer (mCRC) receiving FOLFOX (5-fluorouracil, leucovorin, oxaliplatin), a study presented at the 2016 Gastrointestinal Cancers Symposium in San Francisco, CA has shown.1

Although FOFLOX and FOLFIRI (5-fluorouracil, leucovorin, irinotecan) are effective as first-line treatment, FOLFOX may be more effective in the second-line setting. Furthermore, it is unclear whether cetuximab, which has similar activity across all treatment lines unlike bevacizumab, may be a better option in the third-line setting.

Therefore, researchers sought to compare 2 different treatment sequences of cetuximab and FOLFOX in patients with mCRC who were refractory to frontline FOLFIRI plus bevacizumab.

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For the phase 3 trial, investigators randomly assigned 110 patients to receive second-line irinotecan plus cetuximab followed by third-line FOLFOX-4 (Arm A) or the reverse sequence (Arm B).

Results showed median progression-free survival in Arm A was 9.9 months compared with 11.3 months in Arm B (HR, 0.85; 95% CI, 0.56 – 1.28; P = .427). Median overall survival was 12.3 months and 18.6 months, respectively (HR, 0.79; 95% CI, 0.52 – 1.22; P = .288).

Researchers found that the objective response rate in Arm A was 37% vs 57% in Arm B (P = .05).

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In regard to safety, both treatments were well tolerated, with 2 serious adverse reactions in each arm.

“In RAS wild type patients progressing after a first line bevacizumab-based therapy, cetuximab should be given as first line or third line,” the authors concluded.


  1. Cascinu S, Zaniboni A, Lonardi S, et al. Efficacy of cetuximab immediately after bevacizumab: a phase III multicenter trial comparing two different sequences of cetuximab and FOLFOX in K-Ras WT metastatic colorectal cancer patients refractory FOLFIRI/bevacizumab [abstract]. J Clin Oncol. 2016;34(suppl 4S; abstr 632).