ROCKVILLE, Maryland—The Food and Drug Administration (FDA) has approved Tarceva tablets (erlotinib, OSI Pharmaceuticals) as a single-agent treatment for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) whose disease has continued to progress despite other therapies, including at least one prior chemotherapy regimen. The FDA granted marketing approval on the basis of increased survival findings in the Tarceva-treated arm of a phase III trial in patients who had received second- or third-line therapy for advanced NSCLC. The primary endpoint of the study was overall survival. Secondary endpoints included progression-free survival and tumor response rate. Tarceva, developed by OSI and distributed by Genentech, is an epidermal growth factor receptor (EGFR) inhibitor, and it is the first of the class to demonstrate a survival advantage for advanced NSCLC in a phase III trial. However, two large, randomized studies of Tarceva given concurrently with doublet platinum-based chemotherapy in previously untreated advanced NSCLC failed to show clinical benefit, and the drug is not recommended for such use. The pivotal study involved 731 patients with locally advanced or metastatic NSCLC in a randomized, double-blind, placebo-controlled trial conducted in 17 countries. Patients were randomized 2:1 to receive Tarceva 150 mg or placebo, administered orally once daily until disease progression or unacceptable toxicity. Survival, progression-free survival, and tumor response all proved significant in favor of Tarceva (P < .001). Median survival, evaluated in an intent-to-treat population, was 6.7 months for Tarceva vs 4.7 months for placebo. Median progression-free survival was 9.9 vs 7.9 weeks, respectively, and the Tarceva-treated patients had a tumor response rate of 8.9% vs 0.9% for placebo. One-year survival was 31.2% in the treatment group vs 21.5% for the control patients, and median duration of response was 34.3 vs 15.9 weeks, respectively. EGFR status was not part of the study protocol, and survival was seen in a broad range of patients. Survival among EGFR-positive patients was looked at retrospectively, however. Among the 238 patients with a known EGFR status, the 78 EGFR-positive Tarceva-treated patients had a better survival rate than the 49 EGFR-positive placebo patients. Tarceva did not appear to affect survival in the EGFRnegative subgroup (HR = 1.01). A survival benefit due to Tarceva in the EGFR-negative subgroup cannot be excluded, however, because the confidence intervals for the EGFR-positive, -negative, and unmeasured subgroups are wide and overlap (see Table 1). The most common adverse reactions in patients receiving Tarceva were rash and diarrhea.