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

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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

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N-(4-(3-amino-1H-indazol-4-yl)phenyl)-N1-(2-fluoro-5-methylphenyl)urea
Non-Small Cell Lung Carcinoma
Disease-Free Survival
Hypertension
Safety
Platelet-Derived Growth Factor Receptors
Survival
Appetite
Proteinuria
Nausea
Vascular Endothelial Growth Factor A
Fatigue

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Phase 2 trial of linifanib (ABT-869) in patients with advanced non-small cell lung cancer. / Tan, Eng Huat; Goss, Glenwood D.; Salgia, Ravi; Besse, Benjamin; Gandara, David R; Hanna, Nasser H.; Yang, James Chih Hsin; Thertulien, Raymond; Wertheim, Michael; Mazieres, Julien; Hensing, Thomas; Lee, Christa; Gupta, Neeraj; Pradhan, Rajendra; Qian, Jiang; Qin, Qin; Scappaticci, Frank A.; Ricker, Justin L.; Carlson, Dawn M.; Soo, Ross A.

In: Journal of Thoracic Oncology, Vol. 6, No. 8, 08.2011, p. 1418-1425.

Research output: Contribution to journalArticle

Tan, EH, Goss, GD, Salgia, R, Besse, B, Gandara, DR, Hanna, NH, Yang, JCH, Thertulien, R, Wertheim, M, Mazieres, J, Hensing, T, Lee, C, Gupta, N, Pradhan, R, Qian, J, Qin, Q, Scappaticci, FA, Ricker, JL, Carlson, DM & Soo, RA 2011, 'Phase 2 trial of linifanib (ABT-869) in patients with advanced non-small cell lung cancer', Journal of Thoracic Oncology, vol. 6, no. 8, pp. 1418-1425. https://doi.org/10.1097/JTO.0b013e318220c93e
Tan, Eng Huat ; Goss, Glenwood D. ; Salgia, Ravi ; Besse, Benjamin ; Gandara, David R ; Hanna, Nasser H. ; Yang, James Chih Hsin ; Thertulien, Raymond ; Wertheim, Michael ; Mazieres, Julien ; Hensing, Thomas ; Lee, Christa ; Gupta, Neeraj ; Pradhan, Rajendra ; Qian, Jiang ; Qin, Qin ; Scappaticci, Frank A. ; Ricker, Justin L. ; Carlson, Dawn M. ; Soo, Ross A. / Phase 2 trial of linifanib (ABT-869) in patients with advanced non-small cell lung cancer. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 8. pp. 1418-1425.
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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.",
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AU - Tan, Eng Huat

AU - Goss, Glenwood D.

AU - Salgia, Ravi

AU - Besse, Benjamin

AU - Gandara, David R

AU - Hanna, Nasser H.

AU - Yang, James Chih Hsin

AU - Thertulien, Raymond

AU - Wertheim, Michael

AU - Mazieres, Julien

AU - Hensing, Thomas

AU - Lee, Christa

AU - Gupta, Neeraj

AU - Pradhan, Rajendra

AU - Qian, Jiang

AU - Qin, Qin

AU - Scappaticci, Frank A.

AU - Ricker, Justin L.

AU - Carlson, Dawn M.

AU - Soo, Ross A.

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N2 - 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.

AB - 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.

KW - Angiogenesis

KW - Linifanib (ABT-869)

KW - NSCLC

KW - PDGFR

KW - VEGFR

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