Approval summary for erlotinib for treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen.

Purpose: To describe the Food and Drug Administration (FDA) review and approval of erlotinib (Tarceva, OSI Pharmaceuticals, Melville, NY) for treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen.

Experimental Design: The FDA reviewed raw data in electronic format from a randomized controlled clinical trial comparing erlotinib with placebo in patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.

Results: Patients were randomized in a 2:1 ratio (erlotinib, n = 488 and placebo, n = 243). Erlotinib was superior to placebo for survival, progression-free survival, and tumor response rate. Exploratory analyses indicate that epidermal growth factor receptor status may be an important predictor of the erlotinib survival effect. Rash (75% versus 17%) and diarrhea (54% versus 18%) in the erlotnib and placebo group respectively were the most common adverse events. Severe rash occurred in 9% and severe diarrhea in 6% of erlotinib-treated patients and each resulted in study discontinuation in 1% of patients. Dose reductions were required for 10% of patients with rash and 4% of patients with diarrhea.

Conclusions: On November 18, 2004, the FDA granted erlotinib regular approval for treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. The applicant has committed to conduct post-marketing clinical trials to assess further the effect of epidermal growth factor receptor expression, measured with immunohistochemical staining, on erlotinib treatment effect.