A phase II open-label trial to evaluate the efficacy and toxicity of erlotinib in women with metastatic, hormone receptor-negative, and HER2-negative breast cancer.

296 Background: There is limited success with current therapies for triple negative (TN) breast cancer. Epidermal growth factor receptor (EGFR) is a therapeutic target in solid tumors. Overexpression of EGFR has been linked to an aggressive breast tumor phenotype with a poor prognosis. Previous work at RUSH showed that 64% of 66 TN tumors were EGFR positive (Siziopikou SABCS 2004). To date, the use of EGFR tyrosine kinase inhibitors (TKIs) in metastatic breast cancer (MBC) has been disappointing. These trials enrolled refractory patients and did not select for EGFR expression. We hypothesized that if selected for EGFR expression, there may be a cohort of TN MBC patients who benefit from an EGFR TKI. This is a phase II study of erlotinib in TN-EGFR-positive MBC. Methods: Eligible patients had TN-EGFR-positive MBC. EGFR positivity was defined as staining in >10% of tumor cells by IHC (Dako). Patients required measurable disease, prior treatment with anthracycline and taxane (adjuvant or metastatic setting) and ≤1 prior chemotherapy for MBC. Patients received erlotinib 150mg daily. Primary endpoint was progression-free survival (PFS). Initially, 18 patients were to be accrued. If ≥ 3 patients were progression-free at 4 months, accrual would continue to 43. Results: The study was terminated prematurely due to poor accrual. In total, 11 patients enrolled, 10 were treated. Mean age 56.7y, 18% African-American. Four patients had prior chemotherapy for MBC. Most patients progressed rapidly, median PFS was 29 days (95% CI 25.90 – 32.10). However, 2 patients had stable disease for 225 and 476 days. Treatment was well-tolerated. Toxicities in the 2 patients with stable disease included grade 2 rash, grade 1 diarrhea, grade 1 nausea, grade 2 weight loss and grade 1 diarrhea. Conclusions: Although most patients progressed rapidly, 2/10 patients had prolonged stable disease. This suggests there may be a subset of TN, EGFR positive MBC for whom EGFR-directed therapy may be suitable or that the natural history of their disease was indolent. Future studies to determine molecular and clinical profiles of patients likely to benefit from EGFR-TKI therapy in this population are warranted.