Originally published as JCO Early Release 10.1200/JCO.2008.18.6015 on March 30 2009

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Vandetanib Versus Gefitinib in Patients With Advanced Non–Small-Cell Lung Cancer: Results From a Two-Part, Double-Blind, Randomized Phase II Study

From the Cedars-Sinai Outpatient Cancer Center, Los Angeles; Sharp Memorial Hospital, San Diego, CA; Washington University Medical School; St John's Mercy Medical Center, St Louis, MO; Memorial Sloan-Kettering Cancer Center, New York, NY; Centro Oncológico de Integración Regional, Mendoza, Argentina; University Hospital of Antwerp, Antwerp, Belgium; Universitatsklinikum of the University of Duisburg-Essen, Essen, Germany; AstraZeneca, Macclesfield; and Christie Hospital, Manchester, United Kingdom.

Corresponding author: Ronald B. Natale, MD, Cedars-Sinai Outpatient Cancer Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA; e-mail: Ronald.Natale{at}cshs.org.

Purpose Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) signaling. In this two-part phase II study, the efficacy and safety of vandetanib was compared with that of gefitinib, an inhibitor of EGFR signaling.

Patients and Methods Patients (N = 168) with locally advanced or metastatic (stage IIIB/IV) non–small-cell lung cancer (NSCLC), after failure of first-line with or without second-line platinum-based chemotherapy, received once-daily vandetanib 300 mg (n = 83) or gefitinib 250 mg (n = 85) until disease progression or evidence of toxicity (part A). After a 4-week washout period, eligible patients had the option to switch to the alternative treatment (part B). Progression-free survival (PFS) was the primary efficacy assessment in part A, which was designed to have a higher than 75% power to detect a 33% prolongation of PFS at a one-sided significance level of .2.

Results In part A, vandetanib prolonged PFS compared with gefitinib (hazard ratio = 0.69; 95% CI, 0.50 to 0.96; one-sided P = .013). Patients receiving vandetanib experienced adverse events that were manageable and generally consistent with inhibition of EGFR and VEGFR signaling, including diarrhea, rash, and hypertension. There were no unexpected safety findings with gefitinib. Overall survival, a secondary assessment, was not significantly different between patients initially randomly assigned to either vandetanib or gefitinib.

Conclusion The primary efficacy objective was achieved, with vandetanib demonstrating a significant prolongation of PFS versus gefitinib. Vandetanib 300 mg/d is currently being evaluated as a monotherapy in two randomized phase III studies in advanced NSCLC.

Supported by AstraZeneca. Zactima and Iressa are trademarks of the AstraZeneca group of companies.

Presented in part at the 11th World Conference on Lung Cancer, Barcelona, Spain, June 3-6, 2005; at the European Cancer Conference, Paris, France, October 30 to November 3, 2005; and at the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, June 2-6, 2006.

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

Clinical trial information can be found for the following: NCT00059722.

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