Lay Summary: Erbitux with Avastin is a promising but investigational therapy at this time.

On February 12, 2004, the FDA approved cetuximab (Erbitux) under its accelerated approval program as a combination treatment with irinotecan for the treatment of patients with metastatic colorectal cancer; or alone if patients cannot tolerate irinotecan. The approval of cetuximab by the FDA was largely based on the findings of a randomized, controlled study with 329 patients – 218 for cetuximab plus irinotecan combination therapy and 111 for cetuximab monotherapy. Furthermore, cetuximab was examined as a single agent in a third clinical study with 57 patients. Safety data from the 111 patients treated only with cetuximab was also assessed. All of the studies included patients with EGFR-expressing metastatic colorectal cancer, whose disease had progressed after receiving irinotecan. Results of these trials showed that the combination treatment of cetuximab and irinotecan shrank tumors in 22.9 % of patients and delayed tumor growth by 4.1 months. For patients who received cetuximab alone, the tumor response rate was 10.8 % and tumor growth was delayed by 1.5 months. However, it should be noted that although cetuximab has been reported to shrink tumors in some patients and delay tumor growth, especially when used as a combination treatment, it has not been shown to increase survival.Thierefore, irinotecan and Erbitux and standard for second line therapy or later lines of therapy for colon cancer, as per guideline recommendations, such as NCCN.

Recently MSKCC researchers reported a combination of cetuximab and Avastin.This trial included 83 patients with advanced colorectal cancer who did not respond to treatment with Camptosar alone. No patients had received prior therapy with Erbitux or Avastin. One group of patients was treated with Erbitux/Avastin/Camptosar, and the other group was treated with Erbitux and Avastin.

• Time to cancer progression was 7.3 months for patients treated with Erbitux/Avastin/Camptosar versus 4.9 months for those treated with Erbitux/Avastin.
• Anticancer responses were achieved in 37% of patients treated with Erbitux/Avastin/Camptosar versus 20% for those treated with Erbitux/Avastin.
• Overall survival was 14.5 months for patients treated with Erbitux/Avastin/Camptosar compared with 11.4 months for those treated with Erbitux/Avastin.

The researchers concluded that, when compared to historical data including Erbitux alone, the addition of Avastin to Erbitux plus Camptosar or to Erbitux alone appears to enhance effectiveness in the treatment of advanced colorectal cancer among patients who do not respond to Camptosar. As well, the addition of Camptosar to Avastin and Erbitux appears to provide improved anticancer activity over that of Avastin and Erbitux alone.

Cohen RB. Epidermal growth factor receptor as a therapeutic target in colorectal cancer. Clin Colorectal Cancer. 2003;2(4):246-251.

O’Neil BH, Goldberg RM. Novel chemotherapeutic and targeted agents in metastatic colorectal cancer: The time has arrived. Expert Opin Investig Drugs. 2003;12(12):1939-1949.
Saltz L, Lenz H-J, Kindler H, et al. Randomized Phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: The BOND-2 Study. Journal of Clinical Oncology. 2007;25:4557-4561.