Lee, Jin Soo; Hirsh, Vera; Park, Keunchil; Qin, Shukui; Blajman, Cesar R; Perng, Reury-Perng; Chen, Yuh-Min; Emerson, Laura; Langmuir, Peter; Manegold, Christian
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
2012Apr ; 30 ( 10 ) :1114-21.
PMID : 22370318
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Lee, Jin Soo -
Hirsh, Vera -
Park, Keunchil -
Qin, Shukui -
Blajman, Cesar R -
Perng, Reury-Perng -
Chen, Yuh-Min -
Emerson, Laura -
Langmuir, Peter -
Manegold, Christian -
ABSTRACT
PURPOSE: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor (EGFR), and RET signaling. This placebo-controlled trial assessed whether vandetanib conferred an overall survival benefit in patients with advanced non-small-cell lung cancer (NSCLC) after prior treatment with an EGFR tyrosine kinase inhibitor and one or two chemotherapy regimens. PATIENTS AND
METHODS: Eligible patients were randomly assigned 2:1 to receive vandetanib 300 mg/d or placebo until disease progression or unacceptable toxicity. The primary objective was to compare the outcomes between the two arms with respect to overall survival.
RESULTS: Overall, 924 patients received vandetanib (n = 617) or placebo (n = 307). No significant increase in overall survival was detected in the vandetanib cohort compared with placebo (hazard ratio = 0.95; 95.2% CI, 0.81 to 1.11; P = .527); median overall survival was 8.5 months versus 7.8 months for vandetanib and placebo patients, respectively. Statistically significant advantages favoring vandetanib were observed for progression-free survival (hazard ratio = 0.63; P < .001) and objective response rate (2.6% v 0.7%; P = .028). Postprogression therapy was balanced across the cohorts in both number and type. Adverse events were generally consistent with previous NSCLC studies of vandetanib 300 mg; common events occurring with a greater frequency in the vandetanib arm versus placebo included diarrhea (46% v 11%), rash (42% v 11%), and hypertension (26% v 3%). CONCLUSION: The study did not demonstrate an overall survival benefit for vandetanib versus placebo. There was a higher incidence of some adverse events with vandetanib.
Adult; Aged; Aged, 80 and over; Antineoplastic Agents/adverse effects/*therapeutic use; Carcinoma, Non-Small-Cell Lung/*drug therapy/secondary; Disease-Free Survival; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms/*drug therapy/pathology; Male; Middle Aged; Neoplasm Staging; Odds Ratio; Piperidines/adverse effects/*therapeutic use; Protein-Tyrosine Kinases/*antagonists & inhibitors; Quinazolines/adverse effects/*therapeutic use; Receptor, Epidermal Growth Factor/*antagonists & inhibitors/metabolism; Smoking/adverse effects; Treatment Outcome
MESH
Adult, Aged, Aged, 80 and over, Antineoplastic Agents/adverse effects/*therapeutic use, Carcinoma, Non-Small-Cell Lung/*drug therapy/secondary, Disease-Free Survival, Double-Blind Method, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms/*drug therapy/pathology, Male, Middle Aged, Neoplasm Staging, Odds Ratio, Piperidines/adverse effects/*therapeutic use, Protein-Tyrosine Kinases/*antagonists & inhibitors, Quinazolines/adverse effects/*therapeutic use, Receptor, Epidermal Growth Factor/*antagonists & inhibitors/metabolism, Smoking/adverse effects, Treatment Outcome
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