TY - JOUR
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 D.
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.
AB - 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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U2 - 10.1200/JCO.2007.14.5375
DO - 10.1200/JCO.2007.14.5375
M3 - Article
C2 - 18347007
AN - SCOPUS:42949148257
SN - 0732-183X
VL - 26
SP - 1810
EP - 1816
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 11
ER -