A randomized, phase II study of vandetanib maintenance for advanced or metastatic non-small-cell lung cancer following first-line platinum-doublet chemotherapy.

Abstract

BACKGROUND:

This randomized, phase II study investigated whether benefit could be obtained by giving vandetanib, an oral inhibitor of vascular endothelial and epithelial growth factor receptor, as a maintenance treatment in non-small cell lung cancer (NSCLC).

METHODS:

Patients were randomly assigned to either vandetanib or placebo after completion of 4 cycles of first-line chemotherapy. A progression-free survival (PFS) rate at 3 months was selected as the primary endpoint. We set a maximum PFS rate at 3 months to 30% (null hypothesis), and a minimum PFS rate at 3 months to 50% (alternative hypothesis).

RESULTS:

At the interim analysis, 9 of 24 patients in the vandetanib arm were progression-free at 3 months, whereas 7 of 24 in the placebo arm were progression-free. The placebo arm was closed at the first stage. The vandetanib arm proceeded to the second stage, and recruited a total of 75 patients. At the second stage, 28 out of 63 evaluable patients receiving vandetanib achieved PFS at 3 months. The alternative hypothesis that the PFS rate at 3 months is at least 50% was accepted. The median PFS was 2.7 months (95% CI, 1.9-4.4 months) in the vandetanib arm and 1.7 months (95% CI, 0.9-2.6 months) in the placebo arm. The most common adverse events in patients receiving vandetanib were rash (77.3%) and diarrhea (60.0%).

CONCLUSIONS:

Maintenance therapy with vandetanib for patients with NSCLC after standard platinum doublet chemotherapy is well tolerated and may prolong PFS compared with placebo, and needs additional investigation.

• Authors: Jin Seok Ahn, Ki Hyeong Lee, Jong-Mu Sun, Keunchil Park, Eun-Suk Kang, Eun Kyung Cho, Dae Ho Lee, Sang-We Kim, Gyeong-Won Lee, Jin-Hyoung Kang, Jong-Seok Lee, Jae-Won Lee, Myung-Ju Ahn
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 82 Issue 3 Pg. 455-60 (Dec 2013) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 24075125 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Piperidines
• Platinum Compounds
• Quinazolines
• Vascular Endothelial Growth Factor A
• vandetanib

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality)
• Diarrhea (etiology)
• Disease-Free Survival
• Exanthema (etiology)
• Female
• Humans
• Lung Neoplasms (drug therapy, mortality)
• Maintenance Chemotherapy (methods)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Piperidines (administration & dosage, adverse effects)
• Platinum Compounds (administration & dosage, adverse effects)
• Quinazolines (administration & dosage, adverse effects)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)