Originally published as JCO Early Release 10.1200/JCO.2005.03.1997 on October 24 2005

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Multicenter Phase I/II Study of Cetuximab With Paclitaxel and Carboplatin in Untreated Patients With Stage IV Non–Small-Cell Lung Cancer

From the Division of Medical Oncology and Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Aurora, CO; Indiana University, Indianapolis, IN; Bendheim Cancer Center, Greenwich, CT; and ImClone Systems Incorporated, Branchburg, NJ.

Address reprint requests to Karen Kelly, MD, Health Sciences Center, University of Colorado at Denver, 12801 East 17th Ave, Aurora, CO 80010; e-mail: karen.kelly{at}uchsc.edu

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have demonstrated antitumor activity in patients with non–small-cell lung cancer (NSCLC). This study examined the safety profile of the monoclonal antibody EGFR inhibitor, cetuximab, when added to paclitaxel and carboplatin in untreated patients with stage IV NSCLC. Secondary objectives included efficacy and paclitaxel and carboplatin pharmacokinetics during cetuximab treatment.

PATIENTS AND METHODS: Patients with tumor evidence of EGFR by immunohistochemistry, performance status of 0 to 2, and measurable disease received paclitaxel 225 mg/m² with carboplatin area under the curve = 6 on day 1 every 3 weeks. Cetuximab was administered at 400 mg/m², 1 week before paclitaxel and carboplatin, then weekly at 250 mg/m². The regimen continued until disease progression or intolerable toxicity.

RESULTS: Thirty-one of 32 enrolled patients were treated. The most common cetuximab toxicity was rash in 84% of patients (grade 3 in 13%). Pharmacokinetic sampling did not reveal an interaction between carboplatin, paclitaxel, and cetuximab. An objective response was observed in eight patients (26%). With a median follow-up of 19 months, the median time to progression was 5 months, median survival was 11 months, and the 1- and 2-year survival rates were 40% and 16%, respectively.

CONCLUSION: The combination of cetuximab, paclitaxel, and carboplatin was safe and well tolerated in this population of stage IV patients. The response rate, time to progression, and median survival were slightly superior to historical controls treated with paclitaxel and carboplatin alone. A randomized phase II trial has completed accrual.

Supported by a grant from ImClone Systems Incorporated.

Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, May 31-June 3, 2003, Chicago, IL.

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

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