A Phase 2 Trial of Erlotinib in Patients With Previously Treated Squamous Cell and Adenocarcinoma of the Esophagus

BACKGROUND: Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR) have activity in solid tumors. The authors evaluated an oral EGFR TKI, erlotinib, in patients with previously treated esophageal cancer. METHODS: Thirty patients with measurable, metastatic cancer of the esophageal and gastroesophageal junction received 150 mg erlotinib daily. EGFR-negative tumors (6 patients; 20%) and EGFR-over expressing tumors (24 patients; 80%) were treated. Most patients were men (70%) with adenocarcinoma (57%) and had received previous chemotherapy (97%). RESULTS: Two partial responses were observe d in the EGFR-positive cohort (2 of 24 patients; 8%), and no responses were observed in the EGFR-negative cohort (0 of 6 patients). Reponses were limited to patients who had squamous cell carcinoma (2 of 13 patients; 15%; response duration, 5.5-7 months). The time to tumor progression was longer in patients who had squamous cell carcinoma (3.3 months; range, 1-24 months) compared with patients who had adenocarcinoma (1.6 months; range, 1-6 months; P = .026). Therapy was tolerable with the expected toxicity of skin rash (grade 1-2, 67%; grade 3, 10%). CONCLUSIONS: Erlotinib had limited activity in patients with esophageal cancer, and responses and some protracted stable disease were observed in those with squamous cell carcinoma. Efficacy according to EGFR status could not be assessed given the rarity of EGFR-negative tumors. The current results indicated that further evaluation of this agent in squamous cell carcinoma is warranted. Cancer 2011; 117: 1409-14. (C) 2010 American Cancer Society.