Phase 2 trial of linifanib (ABT-869) in patients with advanced non-small cell lung cancer

Eng Huat Tan, Glenwood D. Goss, Ravi Salgia, Benjamin Besse, David R. Gandara, Nasser H. Hanna, James Chih Hsin Yang, Raymond Thertulien, Michael Wertheim, Julien Mazieres, Thomas Hensing, Christa Lee, Neeraj Gupta, Rajendra Pradhan, Jiang Qian, Qin Qin, Frank A. Scappaticci, Justin L. Ricker, Dawn M. Carlson, Ross A. Soo

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

This study assessed activity and safety of linifanib (ABT-869), a selective inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors, in patients with locally advanced or metastatic non-small cell lung cancer. Methods: In this open-label trial (NCT00517790), patients who received one to two prior lines of systemic therapy were randomized to oral linifanib 0.10 mg/kg (low dose) or 0.25 mg/kg (high dose) once daily. Tumor responses were assessed by independent central imaging review every 8 weeks. The primary end point was progression-free rate at 16 weeks. Secondary end points included objective response rate, time to progression, progression-free survival, and overall survival. Safety was also assessed. Results: Between August 2007 and October 2008, 139 patients were enrolled; 60% had two or more prior regimens, and 88% had nonsquamous cell carcinoma. The objective response rate (low dose and high dose) was 5.0% (3.1 and 6.8%), progression-free rate at 16 weeks was 33.1% (32.3 and 33.8%), median time to progression was 3.6 months (3.6 and 3.7 months), median progression-free survival was 3.6 months (3.5 and 3.6 months), and median overall survival was 9.0 months (10.0 and 8.3 months). The most common linifanib-related adverse events were fatigue (42%), decreased appetite (38%), hypertension (37%), diarrhea (32%), nausea (27%), palmar-plantar erythrodysesthesia (24%), and proteinuria (22%). These events were more common in the high-dose group. The most common linifanib-related grade 3 or 4 adverse event was hypertension (14%). Conclusions: Linifanib is active in advanced non-small cell lung cancer as second- or third-line therapy. Increased adverse event rates were observed at the high dose of linifanib.

Original languageEnglish (US)
Pages (from-to)1418-1425
Number of pages8
JournalJournal of Thoracic Oncology
Volume6
Issue number8
DOIs
StatePublished - Aug 2011

Keywords

  • Angiogenesis
  • Linifanib (ABT-869)
  • NSCLC
  • PDGFR
  • VEGFR

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Tan, E. H., Goss, G. D., Salgia, R., Besse, B., Gandara, D. R., Hanna, N. H., Yang, J. C. H., Thertulien, R., Wertheim, M., Mazieres, J., Hensing, T., Lee, C., Gupta, N., Pradhan, R., Qian, J., Qin, Q., Scappaticci, F. A., Ricker, J. L., Carlson, D. M., & Soo, R. A. (2011). Phase 2 trial of linifanib (ABT-869) in patients with advanced non-small cell lung cancer. Journal of Thoracic Oncology, 6(8), 1418-1425. https://doi.org/10.1097/JTO.0b013e318220c93e