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Title: Cabozantinib in Patients With Advanced Prostate Cancer: Results of a Phase II Randomized Discontinuation Trial
Authors: Smith, David C ×
Smith, Matthew R
Sweeney, Christopher
Elfiky, Aymen A
Logothetis, Christopher
Corn, Paul G
Vogelzang, Nicholas J
Small, Eric J
Harzstark, Andrea L
Gordon, Michael S
Vaishampayan, Ulka N
Haas, Naomi B
Spira, Alexander I
Lara, Primo N
Lin, Chia-Chi
Srinivas, Sandy
Sella, Avishay
Schöffski, Patrick
Scheffold, Christian
Weitzman, Aaron L
Hussain, Maha #
Issue Date: Feb-2013
Publisher: Grune & Stratton
Series Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol:31 issue:4 pages:412-9
Abstract: PURPOSECabozantinib (XL184) is an orally bioavailable tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2. We evaluated the activity of cabozantinib in patients with castration-resistant prostate cancer (CRPC) in a phase II randomized discontinuation trial with an expansion cohort. PATIENTS AND METHODSPatients received 100 mg of cabozantinib daily. Those with stable disease per RECIST at 12 weeks were randomly assigned to cabozantinib or placebo. Primary end points were objective response rate at 12 weeks and progression-free survival (PFS) after random assignment.ResultsOne hundred seventy-one men with CRPC were enrolled. Random assignment was halted early based on the observed activity of cabozantinib. Seventy-two percent of patients had regression in soft tissue lesions, whereas 68% of evaluable patients had improvement on bone scan, including complete resolution in 12%. The objective response rate at 12 weeks was 5%, with stable disease in 75% of patients. Thirty-one patients with stable disease at week 12 were randomly assigned. Median PFS was 23.9 weeks (95% CI, 10.7 to 62.4 weeks) with cabozantinib and 5.9 weeks (95% CI, 5.4 to 6.6 weeks) with placebo (hazard ratio, 0.12; P < .001). Serum total alkaline phosphatase and plasma cross-linked C-terminal telopeptide of type I collagen were reduced by ≥ 50% in 57% of evaluable patients. On retrospective review, bone pain improved in 67% of evaluable patients, with a decrease in narcotic use in 56%. The most common grade 3 adverse events were fatigue (16%), hypertension (12%), and hand-foot syndrome (8%). CONCLUSIONCabozantinib has clinical activity in men with CRPC, including reduction of soft tissue lesions, improvement in PFS, resolution of bone scans, and reductions in bone turnover markers, pain, and narcotic use.
URI: 
ISSN: 0732-183X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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