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

作者：Ulrich Gatzemeier, Anna Pluzanska, Aleksandra Szczęsna, Eckhard Kaukel, Jaromı́r Roubec, Flavio De Rosa, Janusz Milanowski, Hanna Karnicka-Mlodkowski, Miloš Pešek, Piotr Serwatowski, Rodryg Ramlau, Terezie Janaskova, Johan Vansteenkiste, János Strausz, Georgy Moiseevich Manikhas, Joachim von Pawel · 发表于：Journal of Clinical Oncology · 年份：2007 · DOI：10.1200/jco.2005.05.1474 · 被引用次数：885 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Lung Cancer Diagnosis and Treatment

PURPOSE: 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). PATIENTS AND METHODS: Patients received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2 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). RESULTS: 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). CONCLUSION: Er...