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

OBJECTIVES:

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.

MATERIALS AND 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).

CONCLUSION:

Pazopanib has limited activity in NSCLC-NS in patients who have experienced disease progression on bevacizumab.

• Authors: Jared M Weiss, Liza C Villaruz, Mark A Socinski, Anastasia Ivanova, Juneko Grilley-Olson, Nirav Dhruva, Thomas E Stinchcombe
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 86 Issue 2 Pg. 288-90 (Nov 2014) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 25201721 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Indazoles
• Pyrimidines
• Sulfonamides
• Bevacizumab
• pazopanib

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Disease Progression
• Female
• Humans
• Indazoles
• Lung Neoplasms (drug therapy, mortality, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Pyrimidines (administration & dosage)
• Sulfonamides (administration & dosage)
• Treatment Outcome