Final Report of the Efficacy and Safety of the Anti-Epidermal Growth Factor Antibody, Cetuximab (IMC-C225), in Combination with Cisplatin in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN) Refractory to Cisplatin Containing-Chemotherapy
Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 18, 2002
Presenter: Merrill S. Kies
Presenter's Affiliation: MC Anderson Cancer Center
Type of Session: Poster
Recurrent squamous cell cancer of the head and neck (SCCHN) is a clinical challenge, especially in the setting of disease that is refractory to platinum-based agents. Less than 5% of these patients will respond to second-line therapy. Epidermal Growth Factor Receptor (EGFR) is expressed by 92% of SCCHN, and the expression of EGFR has been shown to correlate with decreased survival. Monoclonal antibodies have been shown in a variety of pre-clinical systems to inhibit EGFR. Cetuximab (IMC-C225) is a humanized monoclonal antibody to EGFR, and therefore a potential anti-tumor agent in this poor-risk group of SCCHN patients.
Materials and Methods
- Initially this study enrolled 51 patients with stable disease and 23 patients with progressive disease after platinum-based therapy. These patients had previously received a maximum of 200 mg/m2 of platinum.
- Subsequently the study was ammended to include patients who had received up to 450 mg/m2 of platinum, and an additional 56 patients were enrolled, all of whom has progressive disease within 3 months of intial treatment.
- Patients were treated with further Cisplatin, 50 - 75 mg/m2 every third week, and IMC-C225 weekly; 400 mg/m2 initial dose, followed by 250 mg/m2 weekly for 4 weeks.
- Patients were evaluated for toxicity, response rate, and the duration of response.
- The authors further evaluated patients by skin toxicity, a know toxicity of IMC-C225.
- Of the 130 patients enrolled on this trial, 79 had progressive disease.
- Seventy -eight (99%) of these patients experienced at least one adverse event.
- Grade 3 or 4 adverse events included leukopenia (14%), vomiting (6%), nausea (5%), and peripheral neuropathy (3%).
- The most frequently reported adverse events of any grade were nausea (51%), asthenia (49%), acne (39%), rash (38%), vomiting (38%) and pain (35%).
- In the stable disease group, grade 3 and 4 adverse events included asthenia (16%), leukopenia (12%), pain (10%) and dehydratin (10%).
- Efficacy was only reported for the progressive disease group.
- Of 78 evaluable patients in this group, 9 (12%) experienced a partial response, 13 (17%) had stable disease, and 56 (72%) had progessive disease.
- Of the 9 partial responders, 6 had previously received <200 mg/m2 platinum (pre-ammendment) and 3 had received <450 mg/m2 (post-ammendment).
- Of the 13 patients with stable disease, 4 had been enrolled pre-ammendment and 9 post-ammendment.
- Fifteen of the 56 patients who progressed through IMC-C225 treatment were in the pre-ammendment group, and 41 were in the post-ammendment group.
- Of the 25 patient with no skin toxicity, 23 had progressive disease, 1 had stable disease,and 1 had a partial response.
- Of the 53 patients who experienced skin toxicity, 8 had a partial response, 12 had stable disease, and 33 had progressive disease.
- Severe hyper-sensitivity reactions were seen in 5% of the total 130 patients.
- IMC-C225 in combination with cisplatin was tolerated reasonably well.
- The addition of IMC-C225 to cisplatin did not exacerbate the expected cisplatin-realted toxicities.
- The authors conclude that the combination of cisplatin and IMC-C225 is safe and reasonably well tolerated in refractory SCCHN.
- Safety and efficacy in the pre- and post-ammendment groups were not significantly different.
This trial demonstrates the safety and efficacy of IMC-C225, a novel anti-cancer agent, in recurrent SCCHN. These exciting findings have broad clinical implications for this new agent, one of several in a class of monoclonal antibodies directed towards tumor therapy. The next step in evaluating IMC-C225 is a randomized trial, which is already underway at the MD Anderson Cancer Center. In this next trial, patients with intermediate stage SCCHN are randomized to radiation therapy alone (conventional treatment) or radiation therapy plus IMC-C225. Preliminary results of the this trial should be available within the next year.
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