Cetuximab as an add-on to leucovorin, fluorouracil, and oxaliplatin for stage 3 colon cancer adds no benefit

A large randomized multicenter study found no benefit to adding cetuximab (Erbitux) to the standard adjuvant therapy for resected stage 3 colon cancer, according to a study published in JAMA.

The randomized trial involved 2,686 patients aged 18 years or older at multiple institutions across North America with resected stage 3 wild-type KRAS colon cancer.

The adjuvant therapy used in this study is the modified sixth version of leucovorin, fluorouracil, and oxaliplatin (FOLFOX). Adding cetuximab to FOLFOX had been shown to benefit patients who have metastatic wild-type KRAS colon cancer, but not those with mutated KRAS colon cancer. Both treatment groups received mFOLFOX6, consisting of 12 biweekly courses of oxaliplatin (85 mg/m² ) over 2 hours on day 1 with leucovorin (400 mg/m²) and fluorouracil (400 mg/m²) bolus, then 46-hour intravenous fluorouracil (2,400 mg/m²) on days 1 to 2 starting within 10 weeks of surgery. Patients enrolled in the cetuximab group received 400 mg/m² over 2 hours on day 1 of cycle 1, then 250 mg/m² over 1 hour on day 8 (cycle 1) and day 1 and 8 each of cycles 2 through 12.

Cetuximab is indicated for stage 4 colon cancer, cancer that has metastasized beyond the colon, according to Lisa Holle, PharmD, BCOP, assistant clinical professor, department of pharmacy practice, University of Connecticut School of Pharmacy, Farmington, Conn.

Cetuximab is a recombinant, human/mouse chimeric monoclonal antibody that is an epidermal-growth-factor receptor (EGFR) inhibitor. It is usual to test a drug that is effective against advanced cancer in patients whose cancer has not metastasized beyond the colon, Dr Holle said. Sometimes these drugs are found to be effective earlier and sometimes they aren't, she noted.

The published study was accompanied by an editorial that noted that testing drugs in refractory cases first and then in less refractory cases was a time-honored and rational approach, especially in treating colon cancer.

Why there is not benefit to using cetuximab in earlier stages of colon cancer remains to be determined, Dr Holle said.