Erbitux Fails to Improve Survival in Non-Metastatic Colon Cancer

For patients with stage 3 colorectal cancer and normal KRAS gene activity, Erbitux (cetuximab) did not extend survival when added to chemotherapy. The results were unexpected considering Erbitux is recommended for metastatic colorectal cancer patients whose tumors have a normal—as opposed to mutated—KRAS gene.

In the phase 3 study, 909 patients received a chemotherapy regimen known as FOLFOX and 955 patients received FOLFOX plus Erbitux. Three years after treatment, 76 percent of evaluable patients who received chemotherapy alone were free of disease recurrence, compared with 72 percent of patients who also received Erbitux. In addition, overall survival was slightly better in the chemotherapy-alone group (88 percent versus 84 percent).

“What we learn in metastatic disease does not always apply to the adjuvant (post-surgery) setting,” lead researcher Steven Alberts, MD, of the Mayo Clinic College of Medicine in Minnesota, said at a press briefing regarding why Erbitux didn’t work in stage 3 patients with a normal KRAS gene. One reason may be that colorectal cancer in earlier stages has a different biology than later-stage disease, he said. It’s estimated that about 40 percent of colorectal tumors have mutated KRAS, with the remaining 60 percent having normal KRAS.

Adding Erbitux to chemotherapy also resulted in significantly more side effects, including rash, diarrhea, and neutropenia, and fewer patients in that treatment group were able to complete the full course of treatment because of these toxicities.

Given the results, researchers said Erbitux should not be used in patients with resected stage 3 colon cancer. A similar finding with Avastin (bevacizumab) was reported last year at ASCO. While this drug improves survival when added to chemotherapy for advanced colon cancer, it did not lower recurrence in early-stage disease.