ROCKVILLE, Maryland- After priority review, the US Food and Drug Administration (FDA) has approved Tarceva tablets (erlotinib, OSI Pharmaceuticals) as a singleagent 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. "FDA believes it is crucial for cancer patients to have many safe and effective treatment options in their battle against this disease" said Lester M. Crawford, MD, Acting FDA Commissioner. "With the approval of Tarceva, thousands of patients with lung cancer will not only have access to another treatment option, but one that extends life." Tarceva, which is distributed by Genentech, is an epidermal growth factor receptor (EGFR) inhibitor; while it is known to block the tyrosine kinase associated with EGFR, the mechanism of action by which it exerts its clinical benefit is not completely understood. It is the first of its 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 (carboplatin [Paraplatin] and paclitaxel(Drug information on paclitaxel) or gemcitabine(Drug information on gemcitabine) [Gemzar] and cisplatin(Drug information on cisplatin)) to patients with previously untreated advanced NSCLC failed to show clinical benefit, and the drug is not recommended for such use. The pivotal clinical study on which the FDA based its approval decision for Tarceva was conducted by the National Cancer Institute of Canada Clinical Trials Group, based at Queen's University, Kingston, Ontario, Canada, in collaboration with OSI Pharmaceuticals. It involved 731 patients with locally advanced or metastatic NSCLC in a randomized, double-blind, placebocontrolled trial conducted in 17 countries. Patients were randomized 2:1 to Tarceva 150 mg or to placebo, given orally once daily until disease progression or unacceptable toxicity occurred. Study Results The primary endpoint and all secondary endpoints of the trial were met. Survival, progression-free survival, and tumor response all proved to be significant in favor of Tarceva (P = < .001). Median survival time, evaluated in an intent-to-treat population, was 6.7 months for Tarceva vs 4.7 months for placebo. Median progression-free survival time was 9.9 weeks 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 weeks vs 15.9 weeks, respectively. Subgroup Analyses A series of patient subsets of were examined in exploratory univariate analyses. Tarceva's survival effect was similar across most subsets, although in two subsets, a larger survival effect was observed (EGFR-positive patients and patients who never smoked). Among the 238 patients with a known EGFR status, the 78 EGFRpositive Tarceva patients had a better survival rate than the 49 EGFR-posi- tive placebo patients (hazard ratio [HR] = 0.65). Tarceva did not appear to affect survival in the EGFR-negative subgroup (HR = 1.01). A survival benefit due to Tarceva in the EGFRnegative subgroup cannot be excluded, however, because the confidence intervals for the EGFR-positive, -negative, and unmeasured subgroups are wide and overlap (see Table 1). Nonsmokers in the study who were EGFR-positive had a large Tarceva survival benefit (HR = 0.27). Twenty percent (146) of the study participants had never smoked. Tumor responses were observed in all EGFR subgroups. The most common grade 3-4 adverse events in the Tarceva-treated patients were rash (9%) and diarrhea (6%).