Cetuximab Active in Colon Cancer

September 1, 2002

ORLANDO-The chimeric mono-clonal antibody cetuximab (Erbitux, also known as C225, ImClone Systems) has modest single-agent activity in irinotecan (Camptosar)-refractory colorectal cancer expressing epidermal growth factor receptor (EGFR), researchers said at the American Society of Clinical Oncology 38th Annual Meeting (abstract 504).

ORLANDO—The chimeric mono-clonal antibody cetuximab (Erbitux, also known as C225, ImClone Systems) has modest single-agent activity in irinotecan (Camptosar)-refractory colorectal cancer expressing epidermal growth factor receptor (EGFR), researchers said at the American Society of Clinical Oncology 38th Annual Meeting (abstract 504).

The most significant toxicities of cetuximab, which selectively binds to EGFR, are allergic reactions and an acne-like rash, said Leonard Saltz, MD, of Memorial Sloan-Kettering Cancer Center. "As would be expected from a monoclonal antibody, the typical cytotoxic toxicities [ie, hematologic, gastrointestinal] are virtually absent," he said.

One year earlier at ASCO, Dr. Saltz reported that cetuximab was effective in combination with irinotecan in patients with EGFR-positive disease who had already failed prior irinotecan therapy, with a response rate of 22%. This year, he reported a response rate of 10% for cetuximab monotherapy in that setting.

"C225 is active both as a single agent and in combination with CPT-11 [irino-tecan]," Dr. Saltz said. "Further studies will be needed to define optimal strategies for use of this agent."

According to David Cunningham, MD, of the Royal Marsden MHS Trust, London and Surrey, UK, the present study demonstrates "important activity" for cetuximab monotherapy in colorectal cancer resistant to chemotherapy. "The response rate may be lower than when combined with irinotecan," Dr. Cun-ningham said. "However, single-agent cetuximab is well tolerated and may be suitable for a wider range of patients."

Investigators evaluated cetuximab/irinotecan first because in prior preclinical studies, the combination produced tumor regression in colon cancer xenografts, while cetuximab alone appeared less active than the combination (albeit more active than saline control).

"So, it’s perfectly appropriate that we undertook the most interesting combination first," Dr. Saltz said. "But now we need to look at what can happen with cetuximab alone."

Dr. Saltz and his colleagues evaluated cetuximab monotherapy in 57 patients with colorectal cancer that had progressed on irinotecan or irinotecan-based chemotherapy. All had tumors that were immunohistochemically positive for EGFR. Treatment included diphenhydramine premedication plus a cetuximab test dose on the first day of treatment. On that same day, patients received a loading dose of 400 mg/m2 of cetuximab. Subsequently, they received weekly
doses at 250 mg/m2.

Partial responses were seen in 6 patients (10.5%), while 21 (36.8%) had stable disease or a minor response. Median time to progression was 50 days (range, 14 to 211 days). As of the ASCO presentation, median survival had not been reached.

Three patients experienced allergic reactions (two cases were grade 3-4). No neutropenia or thrombocytopenia has been seen. Other adverse effects included diarrhea (25% all grades, 0% grade 3-4) and nausea/vomiting (46% all grades, 4% grade 3-4).

One common toxicity was an acne-like rash (86% of patients, 18% grade 3-4), which investigators now consider a class effect for EGFR inhibitors. Dr. Saltz said it appears to peak 3 to 4 weeks after treatment and then improve spontaneously somewhat. There is no standard, confirmed treatment for this rash. "The application of antibiotics has been tried, but not systematically," he said.