A review of erlotinib--an oral, selective epidermal growth factor receptor tyrosine kinase inhibitor.

IMPORTANCE OF THE FIELD: The epidermal growth factor receptor (EGFR) is a cell surface receptor for EGF and transforming growth factor-alpha which is overexpressed by a number of human tumors. Erlotinib, developed by OSI Pharmaceuticals, is an oral selective EGFR tyrosine kinase inhibitor, the only drug of its class approved for the treatment of locally advanced non-small cell lung cancer (NSCLC) after failure of at least one previous chemotherapy regimen and for first-line treatment of advanced pancreatic cancer with gemcitabine. AREAS COVERED IN THIS REVIEW: Findings from major Phase III studies that led to the approval of erlotinib are summarized in this review. Key aspects of erlotinib clinical pharmacology, dosing in special populations (e.g., smokers), and toxicity are also reviewed. The article also outlines the results of all correlative studies that have been done in clinical trials of patients receiving erlotinib to identify biomarkers that predict response, such as rash, EGFR status of the tumor by immunohistochemistry and activating EGFR mutations. WHAT WILL THE READER GAIN: The reader will have an outline of the landmark trials leading to the approval of this drug and know which ongoing Phase III trials are expected to enhance the knowledge of this drug's activity. The reader will also understand the pharmacologic bases for the recent change in dosing guidelines of erlotinib, and the current knowledge of clinical and laboratory correlates that can serve as surrogates of response. TAKE HOME MESSAGE: This is a well-tolerated oral biologic agent with two approved clinical indications. More studies to individualize therapy and optimize dosing are needed.