Cabozantinib in patients with advanced prostate cancer: Results of a phase II randomized discontinuation trial - Abstract

PURPOSE: Cabozantinib (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 METHODS: Patients 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.

RESULTS: One 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%).

CONCLUSION: Cabozantinib 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.

Written by:
Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, Vogelzang NJ, Small EJ, Harzstark AL, Gordon MS, Vaishampayan UN, Haas NB, Spira AI, Lara PN Jr, Lin CC, Srinivas S, Sella A, Schöffski P, Scheffold C, Weitzman AL, Hussain M.   Are you the author?
David C. Smith and Maha Hussain, University of Michigan, Ann Arbor; Ulka N. Vaishampayan, Wayne State University, Detroit, MI; Matthew R. Smith, Massachusetts General Hospital; Christopher Sweeney and Aymen A. Elfiky, Dana-Farber Cancer Institute, Boston, MA; Christopher Logothetis and Paul G. Corn, The University of Texas MD Anderson Cancer Center; Alexander I. Spira, US Oncology Research, Houston, TX; Nicholas J. Vogelzang, US Oncology Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Eric J. Small and Andrea L. Harzstark, University of California, San Francisco, San Francisco; Christian Scheffold and Aaron L. Weitzman, Exelixis, South San Francisco; Primo N. Lara Jr, University of California Davis Comprehensive Cancer Center, Sacramento; Sandy Srinivas, Stanford University Medical Center, Stanford, CA; Michael S. Gordon, Pinnacle Oncology Hematology, Scottsdale, AZ; Naomi B. Haas, Abramson Cancer Center, Philadelphia, PA; Alexander I. Spira, Virginia Cancer Specialists, Fairfax, VA; Chia-Chi Lin, National Taiwan University Hospital, Taipei, Taiwan; Avishay Sella, Assaf Harofeh Medical Center, Zerifin, Israel; Patrick Schöffski, University Hospitals Leuven, KU Leuven, Leuven, Belgium.

Reference: J Clin Oncol. 2012 Nov 19. Epub ahead of print.
doi: 10.1200/JCO.2012.45.0494


PubMed Abstract
PMID: 23169517

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