Cetuximab in metastatic colorectal cancer

The authors evaluated the use of cetuximab (Erbitux) as a first-line treatment in those with wild-type (normal) KRAS metastatic colorectal cancer.

Approximately 35% of colorectal cancer patients have metastatic disease (spread of the cancer) at diagnosis and 30-50% of patients with stages II – III cancer develop metastases in the course of the disease, with the liver being the most common site of metastatic disease. The majority of patients with metastatic disease are incurable and can only be offered treatment with palliative (pain-relieving) intent.

Cetuximab is a drug that binds to the epidermal growth factor receptor (an important protein in cell signalling pathways in cancer). Cetuximab blocks the signalling of this receptor to inhibit cell growth while encouraging cell death. Cetuximab has proven to be effective in patients with KRAS (responsible for signalling pathways in cancer) wild-type metastatic colorectal cancer.

This paper reviewed the most relevant clinical trials that have assessed the role of cetuximab as a first-line (primary) treatment of metastatic colorectal cancer.

A phase III trial of 1,198 patients compared cetuximab-FOLFIRI to FOLFIRI alone. FOLFIRI is a chemotherapy regimen consisting of folinic acid, 5-flurouracil and irinotecan (Campto). In patients with wild-type KRAS metastatic cancer, addition of cetuximab to FOLFIRI therapy increased the response rate (percentage of patients who experienced tumor shrinkage) to 57.3% compared to 39.7% for FOLFIRI alone. Progression-free survival (time following treatment before the disease progresses) was 9.9 months for FOLFIRI plus cetuximab compared to 8.4 months for FOLFIRI alone, while overall survival was 23.5 months for FOLFIRI plus cetuximab compared to 20 months for FOLFIRI alone.

In another phase III trial comparing bevacizumab (Avastin)-FOLFIRI (295 patients) to cetuximab-FOLFIRI (297 patients) in metastatic colorectal cancer patients with wild-type KRAS cancer, response rates for cetuximab were 72.2% compared to 63.1% for bevacizumab. There were no statistically significant differences in progression-free survival; however, cetuximab-FOLFIRI significantly prolonged overall survival (28.7 months) compared to bevacizumab-FOLFIRI (25 months).

In a further phase III trial including those with wild-type KRAS, capecitabine plus oxaliplatin (Eloxatin) resulted in a response rate of 64% compared to a response rate of 57% for those taking mFOLFOX6 (leucovorin calcium, 5-fluorouracil and oxaliplatin) . However, there were no significant differences in progression-free survival or overall survival.

However, there are still doubts about when is the right time to use cetuximab or bevacizumab in the treatment of patients with KRAS wild-type metastatic colorectal cancer.

KRAS is a marker that has proved useful in selecting patients eligible to receive cetuximab. According to the authors, the benefit of cetuximab in combination with FOLFIRI as first-line treatment in patients with KRAS wild-type metastatic colorectal cancer has been clearly demonstrated.