title: Clinical and biomarker outcomes of the phase II vandetanib study from the BATTLE trial.
abstract: BACKGROUND
  The Biomarker-integrated Approaches of Targeted Therapy for Lung Cancer Elimination trial prospectively obtained serum and tumor core biopsies and randomized 255 chemorefractory non-small-cell lung cancer (NSCLC) patients into four phase II trials: erlotinib, erlotinib-bexarotene, vandetanib, or sorafenib. Herein, we report the clinical and biomarker results of the phase II vandetanib trial.
  
  
  RESULTS
  Fifty-four patients received vandetanib. The 8-week disease control rate was 33%, median progression-free survival (PFS) 1.81 months, and median overall survival (OS) 6.5 months. No demographic subgroups had PFS or OS benefit. Eight patients with EGFR mutations had a trend for higher 8-week disease control rate (63% versus 31%; p = 0.12) but worse OS (5.9 months versus 9 months; p = 0.8). Patients with EGFR gene amplification (n = 6) had a worse OS (3.9 months versus 9.5 months; p = 0.04). KRAS mutation patients (3.9 months versus 9.5 months; p = 0.23) also had a worse OS. For the serum biomarker analysis, patients with below the median serum expression of interleukin 9c (p = 0.019) and eotaxin (p = 0.007) had a shorter PFS. A trend toward a shorter PFS was also seen in patients with higher than the median neutrophil gelatinase-associated lipocalin (p = 0.079) and lower than the median TNF-related apoptosis-inducing ligand (p = 0.087).
  
  
  CONCLUSIONS
  Our trial results are largely consistent with the literature in unselected pretreated NSCLC patients. Although vandetanib improved median PFS in EGFR mutation patients with epidermal growth factor receptor tyrosine kinase inhibitor-resistance compared with EGFR wild-type, there was no OS advantage. Although vandetanib is no longer in development in NSCLC, identification of a molecular phenotype that responds to dual epidermal growth factor receptor and vascular endothelial growth factor receptor inhibition would contribute to the field.
authors.affiliation: Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center Houston, Texas 7030, USA. astsao@mdanderson.org
authors.forename: Anne S
authors.initials: AS
authors.lastname: Tsao
authors.forename: Suyu
authors.initials: S
authors.lastname: Liu
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Christine M
authors.initials: CM
authors.lastname: Alden
authors.forename: George R
authors.initials: GR
authors.lastname: Blumenschein
authors.forename: Roy
authors.initials: R
authors.lastname: Herbst
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Davis
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.forename: Scott
authors.initials: S
authors.lastname: Lippman
authors.forename: John
authors.initials: J
authors.lastname: Heymach
authors.forename: Hai
authors.initials: H
authors.lastname: Tran
authors.forename: XiMing
authors.initials: X
authors.lastname: Tang
authors.forename: Ignacio
authors.initials: I
authors.lastname: Wistuba
authors.forename: Waun Ki
authors.initials: WK
authors.lastname: Hong
mesh_terms: D000209:Acute-Phase Proteins; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018773:Genes, erbB-1 / Q000235:genetics; D006801:Humans; D016906:Interleukin-9 / Q000097:blood; D053208:Kaplan-Meier Estimate; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood; D018631:ras Proteins / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016906:Interleukin-9; C117307:KRAS protein, human; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D010880:Piperidines; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D053221:TNF-Related Apoptosis-Inducing Ligand; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; C452423:vandetanib