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Single agent IMC-C225 (Erbitux) has activity in CPT-11 refractory colorectal cancer (CRC) that expresses epidermal growth factor receptor (EGFR)

Reviewer: Thomas Dilling, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 19, 2002

Presenter: L. Saltz
Presenter's Affiliation: Memorial Sloan-Kettering Cancer Center
Type of Session: Scientific

Background

• In a previous trial (reported at ASCO last year), IMC-C225, in combination with CPT-11, was demonstrated to have a 22.5% response rate in 120 patients with CRC refractory to CPT-11 treatment.
• A tumor xenograft model of EGFR-expressing CRC demonstrated some benefit of C225 as monotherapy.
• Based upon these results, a study was undertaken to assess activity of IMC-C225 as monotherapy in patients with CPT-11-refractory CRC.

Materials and Methods

• Patients recruited had measurable disease, demonstrated disease progression on CPT-11, and had tumors which expressed EGFR.
• Inclusion criteria required ECOG Performance Status 0-2.
• Intercurrent chemotherapy post CPT-11 failure was an exclusion criterion.
• Time from cancer diagnosis to initiation of the study was a mean of 13 months in these patients.
• Median ECOG performance status was 0, though 20% had a performance status of 2.
• EGFR immunohistochemical staining demonstrated 1+ staining in 30% of patients, 2+ in 53%, and 3+ in 17%.
• 140 patients were recruited; of these, 105 possessed tumors which expressed EGFR.
• Of these, 57 were treated. 44 patients had colonic primary tumor and 13 had rectal tumors.
• Treatment on day #1 included premedication with Benadryl, followed by a 20mg test dose of C225. Patients then received a 400 mg loading dose. They then 250 mg weekly.
• Studied endpoints included analysis of toxicity/tolerability, as well as responsiveness of tumors to treatment.

Results

• The majority of patients (86%) had an acneiform reaction. Eighteen percent of patients experienced grade 3/4 toxicity. This rash was self-limited, typically appearing in week 3-4 of treatment. Treatment with antibiotics did not alter the duration of symptoms.
• The other predominant side effect was allergic reaction, in 5% of patients.
• Other side effects (nausea, vomiting, diarrhea, asthenia) occurred at levels likely attributable to the primary disease process, though no specific attempt was made to further qualify this.
• 6/57 (10.5%) have had a partial response (PR) and 21 (36.8%) have had stable disease (SD) on C225 monotherapy.
• Median duration of response has not been reached.
• Median time to progression (TTP) was 50 days.

Author's Conclusions

• Monotherapy with IMC-C225 is well tolerated in these patients.
• It produced objective responses in patients with treatment-refractory CRC.

Clinical/Scientific Implications

• This is an exciting study which will require validation in a phase 3 trial.
• Many in the oncology community are expecting this drug to make a big impact in the future of cancer care.
• The drug appears to be well tolerated with very mild toxicity.
• Future studies will evaluate the combination of C225 with chemotherapy and radiation therapy regimens for a variety of cancers.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.