A phase II, multicenter study of cetuximab monotherapy in patients with refractory, metastatic colorectal carcinoma with absent epidermal growth factor receptor immunostaining.

PURPOSE: To determine antitumor activity of cetuximab monotherapy in patients with refractory metastatic colorectal carcinoma (mCRC) with lack of specific membrane immunostaining for the epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: Patients had immunohistochemical (IHC)-determined mCRC with absent EGFR immunostaining that progressed after receiving at least one standard, fluoropyrimidine-containing chemotherapeutic regimen. Absent EGFR immunostaining was defined as the IHC absence of specific membrane staining in ≥500 cancer cells examined in well-preserved tissue. The study was performed prior to results of studies linking cetuximab sensitivity to K-ras mutation status. Patients received 400 mg/m(2) of intravenous (i.v.) cetuximab followed by once-weekly i.v. cetuximab 250 mg/m(2) until disease progression or unacceptable toxicity. Patients were evaluated for objective response at least every 6 weeks. Kaplan-Meier estimates were calculated for duration of response, time to progression (TTP), and overall survival (OS).
RESULTS: Seven (8.2%) of 85 mCRC patients whose tumors lacked EGFR immunostaining had major responses following cetuximab treatment. The median duration of response was 5.1 months. Median TTP and OS were 2.5 months and 10.0 months, respectively; the 1-year survival rate was 39.6%. The most frequently reported cetuximab-related adverse events were acneiform dermatitis, fatigue, headache, and dry skin.
CONCLUSION: Cetuximab monotherapy produces objective antitumor activity in patients with mCRC that does not express EGFR as determined by IHC. The activity and safety profiles of cetuximab monotherapy in mCRC lacking EGFR immunostaining are similar to previous observations in EGFR IHC-positive disease that was not selected based on K-ras mutation status.