Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase ii study.
Authors
Natale, Ronald BBodkin, David
Govindan, Ramaswamy
Sleckman, Bethany G
Rizvi, Naiyer A
Capó, Adolfo
Germonpré, Paul
Eberhardt, Wilfried E E
Stockman, Paul K
Kennedy, Sarah J
Ranson, Malcolm R
Affiliation
Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA 90048, USA. Ronald.Natale@cshs.orgIssue Date
2009-05-20
Metadata
Show full item recordAbstract
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.Citation
Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase ii study. 2009, 27 (15):2523-9 J. Clin. Oncol.Journal
Journal of Clinical OncologyDOI
10.1200/JCO.2008.18.6015PubMed ID
19332730Type
ArticleLanguage
enISSN
1527-7755ae974a485f413a2113503eed53cd6c53
10.1200/JCO.2008.18.6015
Scopus Count
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