Originally published as JCO Early Release 10.1200/JCO.2005.02.840 on July 25 2005

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TRIBUTE: A Phase III Trial of Erlotinib Hydrochloride (OSI-774) Combined With Carboplatin and Paclitaxel Chemotherapy in Advanced Non–Small-Cell Lung Cancer

From The University of Texas M.D. Anderson Cancer Center, Houston, TX; University of California Los Angeles, Los Angeles; Kaiser Permanente, Oakland; Genentech Inc, South San Francisco, CA; Georgia Oncology Partners, Marietta, GA; Dana-Farber Cancer Institute, Boston, MA; Vanderbilt-Ingram Cancer Center, Nashville, TN; Memorial Sloan-Kettering Cancer Center, New York, NY, for the TRIBUTE Investigator Group

Address reprint requests to Vincent A. Miller, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021; e-mail: millerv{at}MSKCC.ORG

PURPOSE: Erlotinib is a potent reversible HER1/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with single-agent activity in patients with non–small-cell lung cancer (NSCLC). Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC.

PATIENTS AND METHODS: TRIBUTE randomly assigned patients with good performance status and previously untreated advanced (stage IIIB/IV) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib. Random assignment was stratified by stage, weight loss in the previous 6 months, measurable disease, and treatment center. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response (OR), and duration of response.

RESULTS: There were 1,059 assessable patients (526 erlotinib; 533 placebo). Median survival for patients treated with erlotinib was 10.6 v 10.5 months for placebo (hazard ratio, 0.99; 95% CI, 0.86 to 1.16; P = .95). There was no difference in OR or median TTP. Patients who reported never smoking (72 erlotinib; 44 placebo) experienced improved OS in the erlotinib arm (22.5 v 10.1 months for placebo), though no other prespecified factors showed an advantage in OS with erlotinib. Erlotinib and placebo arms were equivalent in adverse events (except rash and diarrhea).

CONCLUSION: Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC. Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future randomized trials.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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