Phase III Study of Erlotinib in Combination With Cisplatin and Gemcitabine in Advanced Non–Small-Cell Lung Cancer: The Tarceva Lung Cancer Investigation Trial

<jats:sec><jats:title>Purpose</jats:title><jats:p> Erlotinib is a potent inhibitor of the epidermal growth factor receptor tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double-blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of erlotinib in combination with cisplatin and gemcitabine as first-line treatment for advanced non–small-cell lung cancer (NSCLC). </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m<jats:sup>2</jats:sup> on days 1 and 8 and cisplatin 80 mg/m<jats:sup>2</jats:sup> on day 1). The primary end point was overall survival (OS). Secondary end points included time to disease progression (TTP), response rate (RR), duration of response, and quality of life (QoL). </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> A total of 1,172 patients were enrolled. Baseline demographic and disease characteristics were well balanced. There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment arms. In a small group of patients who had never smoked, OS and progression-free survival were increased in the erlotinib group; no other subgroups were found more likely to benefit. Erlotinib with chemotherapy was generally well tolerated; incidence of adverse events was similar between arms, except for an increase in rash and diarrhea with erlotinib (generally mild). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Erlotinib with concurrent cisplatin and gemcitabine showed no survival benefit compared with chemotherapy alone in patients with chemotherapy-naïve advanced NSCLC. </jats:p></jats:sec>