Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva

Objective. To evaluate the efficacy and toxicity of erlotinib in the management of sguamous cell carcinoma (SCC) of the vulva. Methods. Patients with vulvar lesions amenable to surgery or chemoradiation (cohort 1) or those with metastatic measurable disease (cohort 2) received erlotinib 150 mg daily. Patients were monitored for toxicity. Responses were determined by digital photography or RECIST 1.1. Cohort 1 underwent pre and post treatment biopsies. EGFR immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and mutational analysis were performed. Results. 41 patients were enrolled: 17 in cohort 1 and 24 in cohort 2. Notable grade 3 or 4 toxicities included allergic reaction (1), diarrhea/electrolyte abnormalities (3), ischemic colitis (1), and renal failure (3) and electrolyte abnormalities (n = 2). Mean number of cycles for cohort 2 was 3.3. Overall clinical benefit rate was 67.5% with 11 (27.5%) partial responses (PR), 16 (40.0%) stable disease (SD), and 7 (17.5%) progressive disease. Responses were of short duration. All pre and post treatment biopsies exhibited 2-3 + EGFR staining. 5 of 14 patients (35%) were found to have EGFR amplification (n = 3) or high polysomy/trisomy (n = 2). These five patients had either a PR (n = 3) or SD (n = 2). Gain of function mutations were not been identified. Conclusions. This is the first reported controlled trial evaluating erlotinib for the management of vulvar carcinoma. Toxicities were acceptable given the lack of treatment options for these patients. Given the observed clinical benefits erlotinib may represent one of the most active agents available to treat vulvar SCC. (C) 2012 Elsevier Inc. All rights reserved.