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

Lung Cancer. 2013 Dec;82(3):455-60. doi: 10.1016/j.lungcan.2013.08.027. Epub 2013 Sep 8.

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.

Keywords: Chemotherapy; Lung cancer; Maintenance; Progression-free survival; Target therapy; Vandetanib.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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