title: Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. This phase III study assessed the efficacy of vandetanib versus erlotinib in unselected patients with advanced non-small-cell lung cancer (NSCLC) after treatment failure with one to two prior cytotoxic chemotherapy regimens.
  
  
  METHODS
  One thousand two hundred forty patients were randomly assigned to receive vandetanib 300 mg/d (n = 623) or erlotinib 150 mg/d (n = 617). The primary objective was to show superiority in progression-free survival (PFS) for vandetanib versus erlotinib. If the difference did not reach statistical significance for superiority, a noninferiority analysis was conducted.
  
  
  RESULTS
  There was no significant improvement in PFS for patients treated with vandetanib versus erlotinib (hazard ratio [HR], 0.98; 95.22% CI, 0.87 to 1.10; P = .721); median PFS was 2.6 months for vandetanib and 2.0 months for erlotinib. There was also no significant difference for the secondary end points of overall survival (HR, 1.01; P = .830), objective response rate (both 12%), and time to deterioration of symptoms for pain (HR, 0.92; P = .289), dyspnea (HR, 1.07; P = .407), and cough (HR, 0.94; P = .455). Both agents showed equivalent PFS and overall survival in a preplanned noninferiority analysis. Adverse events (AEs; any grade) more frequent with vandetanib than erlotinib included diarrhea (50% v 38%, respectively) and hypertension (16% v 2%, respectively); rash was more frequent with erlotinib than vandetanib (38% v 28%, respectively). The overall incidence of grade ≥ 3 AEs was also higher with vandetanib than erlotinib (50% v 40%, respectively).
  
  
  CONCLUSIONS
  In patients with previously treated advanced NSCLC, vandetanib showed antitumor activity but did not demonstrate an efficacy advantage compared with erlotinib. There was a higher incidence of some AEs with vandetanib.
authors.affiliation: Cedars-Sinai Outpatient Cancer Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. rnatale@cshs.org
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Natale
authors.forename: Sumitra
authors.initials: S
authors.lastname: Thongprasert
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Tsai
authors.forename: Patrapim
authors.initials: P
authors.lastname: Sunpaweravong
authors.forename: David
authors.initials: D
authors.lastname: Ferry
authors.forename: Clive
authors.initials: C
authors.lastname: Mulatero
authors.forename: Robert
authors.initials: R
authors.lastname: Whorf
authors.forename: Joyce
authors.initials: J
authors.lastname: Thompson
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.forename: Peter
authors.initials: P
authors.lastname: Langmuir
authors.forename: Sven
authors.initials: S
authors.lastname: Gogov
authors.forename: Jacqui A
authors.initials: JA
authors.lastname: Rowbottom
authors.forename: Glenwood D
authors.initials: GD
authors.lastname: Goss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001208:Asia; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004311:Double-Blind Method; D000069347:Erlotinib Hydrochloride; D005060:Europe; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009656:North America; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C452423:vandetanib