Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/93449
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Type: Journal article
Title: Cabozantinib in chemotherapy-pretreated metastatic castration-resistant prostate cancer: results of a phase II nonrandomized expansion study
Author: Smith, M.
Sweeney, C.
Corn, P.
Rathkopf, D.
Smith, D.
Hussain, M.
George, D.
Higano, C.
Harzstark, A.
Sartor, A.
Vogelzang, N.
Gordon, M.
De Bono, J.
Haas, N.
Logothetis, C.
Elfiky, A.
Scheffold, C.
Laird, A.
Schimmoller, F.
Basch, E.
et al.
Citation: Journal of Clinical Oncology, 2014; 32(30):3391-3399
Publisher: American Society of Clinical Oncology
Issue Date: 2014
ISSN: 0732-183X
1527-7755
Statement of
Responsibility: 
Matthew R. Smith, Christopher J. Sweeney, Paul G. Corn, Dana E. Rathkopf, David C. Smith, Maha Hussain, Daniel J. George, Celestia S. Higano, Andrea L. Harzstark, A. Oliver Sartor, Nicholas J. Vogelzang, Michael S. Gordon, Johann S. de Bono, Naomi B. Haas, Christopher J. Logothetis, Aymen Elfiky, Christian Scheffold, A. Douglas Laird, Frauke Schimmoller, Ethan M. Basch and Howard I. Scher
Abstract: PURPOSE: Cabozantinib (XL184), an oral inhibitor of multiple receptor tyrosine kinases such as MET and VEGFR2, was evaluated in a phase II nonrandomized expansion study in castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Patients received open-label cabozantinib at daily starting doses of 100 mg or 40 mg until disease progression or unacceptable toxicity. The primary end point was bone scan response, defined as ≥ 30% reduction in bone scan lesion area. Other efficacy end points included overall survival, pain, analgesic use, and biomarkers. RESULTS: One hundred forty-four patients sequentially enrolled in either a 100-mg (n = 93) or 40-mg (n = 51) study cohort. Ninety-one patients (63%) had a bone scan response, often by week 6. Treatment resulted in clinically meaningful pain relief (57% of patients) and reduction or discontinuation of narcotic analgesics (55% of patients), as well as improvements in measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Improvements in each of these outcomes were observed in both cohorts: bone scan response in 73% and 45%, respectively; reductions in measurable soft tissue disease in 80% and 79%, respectively. Median overall survival was 10.8 months for the entire population. Most common grade 3 or 4 adverse events were fatigue (22%) and hypertension (14%). Fewer dose reductions because of toxicity were required in the 40-mg group. CONCLUSION: The evidence suggests that cabozantinib has clinically meaningful activity in CRPC. Cabozantinib resulted in improvements in bone scans, pain, analgesic use, measurable soft tissue disease, circulating tumor cells, and bone biomarkers. Taken together, these phase II observations warrant further development of cabozantinib in prostate cancer.
Keywords: Neoplasm Metastasis
Anilides
Pyridines
Prostate-Specific Antigen
Protein Kinase Inhibitors
Prostatic Neoplasms, Castration-Resistant
Neoplastic Cells, Circulating
Receptor Protein-Tyrosine Kinases
Rights: © 2014 by American Society of Clinical Oncology
DOI: 10.1200/JCO.2013.54.5954
Published version: http://dx.doi.org/10.1200/jco.2013.54.5954
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