Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane

Harold J. Burstein, Anthony D. Elias, Hope S. Rugo, Melody A. Cobleigh, Antonio C. Wolff, Peter D. Eisenberg, Mary Lehman, Bonne J. Adams, Carlo L. Bello, Samuel E. DePrimo, Charles M. Baum, Kathy Miller

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Abstract

Purpose: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC). Patients and Methods: Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis. Results: Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for ≥ 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during ≥ 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions. Conclusion: Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.

Original languageEnglish (US)
Pages (from-to)1810-1816
Number of pages7
JournalJournal of Clinical Oncology
Volume26
Issue number11
DOIs
StatePublished - 2008

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Anthracyclines
Protein-Tyrosine Kinases
Breast Neoplasms
Colony-Stimulating Factor Receptors
sunitinib
taxane
Proto-Oncogene Proteins c-kit
Platelet-Derived Growth Factor Receptors
Vascular Endothelial Growth Factor Receptor
Macrophage Colony-Stimulating Factor
Anorexia
Nausea
Vascular Endothelial Growth Factor A
Multicenter Studies
Fatigue
Diarrhea
Therapeutics
Pharmacokinetics
Biomarkers
Inflammation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. / Burstein, Harold J.; Elias, Anthony D.; Rugo, Hope S.; Cobleigh, Melody A.; Wolff, Antonio C.; Eisenberg, Peter D.; Lehman, Mary; Adams, Bonne J.; Bello, Carlo L.; DePrimo, Samuel E.; Baum, Charles M.; Miller, Kathy.

In: Journal of Clinical Oncology, Vol. 26, No. 11, 2008, p. 1810-1816.

Research output: Contribution to journalArticle

Burstein, HJ, Elias, AD, Rugo, HS, Cobleigh, MA, Wolff, AC, Eisenberg, PD, Lehman, M, Adams, BJ, Bello, CL, DePrimo, SE, Baum, CM & Miller, K 2008, 'Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane', Journal of Clinical Oncology, vol. 26, no. 11, pp. 1810-1816. https://doi.org/10.1200/JCO.2007.14.5375
Burstein, Harold J. ; Elias, Anthony D. ; Rugo, Hope S. ; Cobleigh, Melody A. ; Wolff, Antonio C. ; Eisenberg, Peter D. ; Lehman, Mary ; Adams, Bonne J. ; Bello, Carlo L. ; DePrimo, Samuel E. ; Baum, Charles M. ; Miller, Kathy. / Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 11. pp. 1810-1816.
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abstract = "Purpose: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC). Patients and Methods: Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis. Results: Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11{\%}. Three additional patients (5{\%}) maintained stable disease for ≥ 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52{\%}) required dose interruption during ≥ 1 cycle, and 25 patients required dose reduction (39{\%}). Thirty-six patients (56{\%}) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions. Conclusion: Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.",
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T1 - Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, in patients with metastatic breast cancer previously treated with an anthracycline and a taxane

AU - Burstein, Harold J.

AU - Elias, Anthony D.

AU - Rugo, Hope S.

AU - Cobleigh, Melody A.

AU - Wolff, Antonio C.

AU - Eisenberg, Peter D.

AU - Lehman, Mary

AU - Adams, Bonne J.

AU - Bello, Carlo L.

AU - DePrimo, Samuel E.

AU - Baum, Charles M.

AU - Miller, Kathy

PY - 2008

Y1 - 2008

N2 - Purpose: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating factor-1 receptor. This phase II, open-label, multicenter study evaluated sunitinib monotherapy in patients with metastatic breast cancer (MBC). Patients and Methods: Sixty-four patients previously treated with an anthracycline and a taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off treatment). The primary end point was objective response rate. Plasma samples were obtained for pharmacokinetic and biomarker analysis. Results: Seven patients achieved a partial response (median duration, 19 weeks), giving an overall response rate of 11%. Three additional patients (5%) maintained stable disease for ≥ 6 months. Median time to progression and overall survival were 10 and 38 weeks, respectively. Notably, responses occurred in triple negative tumors and HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required dose interruption during ≥ 1 cycle, and 25 patients required dose reduction (39%). Thirty-six patients (56%) had dose modifications due to adverse events (AEs). Treatment was associated with increases in plasma VEGF and decreases in soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea, mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2) in severity and were effectively managed with dose delays or reductions. Conclusion: Sunitinib is active in patients with heavily pretreated MBC. Most AEs were of mild-to-moderate severity and manageable with supportive treatment and/or dose modification. Further studies in breast cancer are warranted.

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