title: A single-arm phase II trial of pazopanib in patients with advanced non-small cell lung cancer with non-squamous histology with disease progression on bevacizumab containing therapy.
abstract: OBJECTIVE
  Platinum-based chemotherapy with bevacizumab is a standard therapy for patients with stage IIIB/IV non-small cell lung cancer (NSCLC) with non-squamous (NS) histology. Mechanisms of resistance to bevacizumab include increased VEGF signaling or activation of VEGF receptors. Pazopanib is a multi-targeted VEGF receptor tyrosine kinase with single agent activity in NSCLC.
  
  
  METHODS
  Stage IIIB/IV patients with adequate organ function, who progressed on a bevacizumab containing therapy were eligible if it had been ≤8 weeks since the last bevacizumab treatment. The primary end-point was disease control rate (DCR), defined as partial or complete response, or stable disease for ≥12 weeks. Patients were assessed radiographically every 2 cycles (6 weeks). A Simon 2-stage design was used, and if in the first stage ≤4 of 17 patients experienced disease control the trial was to have been stopped for futility. An unplanned analysis was performed after 15 patients were evaluable secondary to slow accrual.
  
  
  RESULTS
  Between December 2010 and November 2013, 15 patients were treated on trial. The median age was 61 years (range 39-74), and all patients had stage IV disease. Of the 15 patients, 4 discontinued therapy prior to cycle 2 evaluation due to adverse events (n=3) and medical illness (n=1), 5 patients had progressive disease, 4 patients had stable disease for <12 weeks, and 2 patients had stable disease for ≥12 weeks. No responses were observed. The DCR observed was 13% (2/15), and the trial did not meet the criteria to proceed to the second stage. Episodes of grade 3 treatment related toxicities observed included: increased ALT (n=2), increased AST (n=1), anorexia (n=3), fatigue (n=3), hypertension (n=1), infection (n=1), mucositis (n=2), nausea (n=3), pericardial effusion (n=1), and vomiting (n=1).
  
  
  CONCLUSIONS
  Pazopanib has limited activity in NSCLC-NS in patients who have experienced disease progression on bevacizumab.
authors.affiliation: University of North Carolina at Chapel Hill, 170 Manning Drive, Physician's Office Building 3rd Floor, Chapel Hill, NC 27599-7305, United States.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Weiss
authors.affiliation: University of North Carolina at Chapel Hill, 170 Manning Drive, Physician's Office Building 3rd Floor, Chapel Hill, NC 27599-7305, United States.
authors.forename: Liza C
authors.initials: LC
authors.lastname: Villaruz
authors.affiliation: University of North Carolina at Chapel Hill, 170 Manning Drive, Physician's Office Building 3rd Floor, Chapel Hill, NC 27599-7305, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.affiliation: University of North Carolina at Chapel Hill, 170 Manning Drive, Physician's Office Building 3rd Floor, Chapel Hill, NC 27599-7305, United States.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.affiliation: University of North Carolina at Chapel Hill, 170 Manning Drive, Physician's Office Building 3rd Floor, Chapel Hill, NC 27599-7305, United States.
authors.forename: Juneko
authors.initials: J
authors.lastname: Grilley-Olson
authors.affiliation: University of North Carolina at Chapel Hill, 170 Manning Drive, Physician's Office Building 3rd Floor, Chapel Hill, NC 27599-7305, United States.
authors.forename: Nirav
authors.initials: N
authors.lastname: Dhruva
authors.affiliation: University of North Carolina at Chapel Hill, 170 Manning Drive, Physician's Office Building 3rd Floor, Chapel Hill, NC 27599-7305, United States. Electronic address: Thomas_stinchcombe@med.unc.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007191:Indazoles; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011743:Pyrimidines / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; D000068258:Bevacizumab; C516667:pazopanib
keywords: Angiogenesis; Clinical trial; Multi-targeted tyrosine kinase inhibitors; Non-small cell lung cancer; Second-line therapy; Targeted therapy