title: Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase ii study.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cedars-Sinai Outpatient Cancer Center, Los Angeles, CA 90048, USA. Ronald.Natale@cshs.org
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Natale
authors.forename: David
authors.initials: D
authors.lastname: Bodkin
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Govindan
authors.forename: Bethany G
authors.initials: BG
authors.lastname: Sleckman
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.forename: Adolfo
authors.initials: A
authors.lastname: Capó
authors.forename: Paul
authors.initials: P
authors.lastname: Germonpré
authors.forename: Wilfried E E
authors.initials: WE
authors.lastname: Eberhardt
authors.forename: Paul K
authors.initials: PK
authors.lastname: Stockman
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Kennedy
authors.forename: Malcolm
authors.initials: M
authors.lastname: Ranson