A phase II trial of cetuximab in high-risk premalignant lesions of the upper aerodigestive tract.

Abstract

5528 Background: High risk head and neck premalignancy includes patients with prior HNSCC and loss of heterozygosity (LOH). These patients demonstrate 30-60% rates of progression to malignancy despite conventional surgical excision. We performed a phase II trial using short term therapy with cetuximab, a humanized monoclonal antibody directed against EGFR, in the treatment of high risk premalignant lesions of the UADT. Methods: Inclusion criteria required; 1) presence of 3p, 9p21, or 17p LOH, and/or 2) surgically unresectable high grade premalignant lesions, and/or 3) high grade premalignancy after curative therapy for HNSCC. Patients received cetuximab 400 mg/m2 on week one followed by 250 mg/m2 on week 2-8 or observation, with the option for crossover to cetuximab for patients originally randomized to the observation arm. Histologic grade (1=benign, 2=mild dysplasia, 3=moderate dysplasia, 4=severe dysplasia/carcinoma in situ, 5=invasive cancer) and change in grade of dysplasia was evaluated. Results: 19 patients were enrolled. Two patients discontinued therapy due to toxicity. We noted a decrease in grade of dysplasia in the cetuximab treated group (-1.0) vs. the observation group (-0.2), (Wilcoxon test p value = 0.18). In the observation group, 0/5 patients (0%) underwent complete resolution of dysplasia; while 4/12 (33.3%) treated patients had no remaining dysplasia after therapy (p = 0.26), three of these patients had complete resolution of dysplastic changes after cetuximab therapy alone. Of these three patients, two have had no recurrence of leukoplakia or dysplasia at 1.5 and 2 years. One patient treated with oral cavity dysplasia has had no recurrence of dysplasia or lesions within the oral cavity, but developed a hypopharyngeal cancer at 1.5 years after trial completion. Of 5 patients randomized to observation, three underwent crossover to cetuximab therapy, and two of these three patients had complete resolution of dysplasia. Conclusions: EGFR blockade with cetuximab alone can result in significant, durable, and complete clinical and histological resolution of moderate to severe dysplasia in at least a subset of high risk patients.