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

David C. Smith, Matthew R. Smith, Christopher Sweeney, Aymen A. Elfiky, Christopher Logothetis, Paul G. Corn, Nicholas J. Vogelzang, Eric J. Small, Andrea L. Harzstark, Michael S. Gordon, Ulka N. Vaishampayan, Naomi B. Haas, Alexander Spira, Primo N. Lara, Chia Chi Lin, Sandy Srinivas, Avishay Sella, Patrick Schöffski, Christian Scheffold, Aaron L. WeitzmanMaha Hussain

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)412-419
Number of pages8
JournalJournal of Clinical Oncology
Volume31
Issue number4
DOIs
StatePublished - Feb 1 2013
Externally publishedYes

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Prostatic Neoplasms
Castration
Disease-Free Survival
Narcotics
Bone and Bones
Placebos
Hand-Foot Syndrome
cabozantinib
Pain
Vascular Endothelial Growth Factor Receptor-2
Bone Remodeling
Protein-Tyrosine Kinases
Fatigue
Alkaline Phosphatase
Hypertension
Serum

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Smith, D. C., Smith, M. R., Sweeney, C., Elfiky, A. A., Logothetis, C., Corn, P. G., ... Hussain, M. (2013). Cabozantinib in patients with advanced prostate cancer: Results of a phase II randomized discontinuation trial. Journal of Clinical Oncology, 31(4), 412-419. https://doi.org/10.1200/JCO.2012.45.0494

Cabozantinib in patients with advanced prostate cancer : Results of a phase II randomized discontinuation trial. / 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; Lara, Primo N.; Lin, Chia Chi; Srinivas, Sandy; Sella, Avishay; Schöffski, Patrick; Scheffold, Christian; Weitzman, Aaron L.; Hussain, Maha.

In: Journal of Clinical Oncology, Vol. 31, No. 4, 01.02.2013, p. 412-419.

Research output: Contribution to journalArticle

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, A, Lara, PN, Lin, CC, Srinivas, S, Sella, A, Schöffski, P, Scheffold, C, Weitzman, AL & Hussain, M 2013, 'Cabozantinib in patients with advanced prostate cancer: Results of a phase II randomized discontinuation trial', Journal of Clinical Oncology, vol. 31, no. 4, pp. 412-419. https://doi.org/10.1200/JCO.2012.45.0494
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 ; Lara, Primo N. ; Lin, Chia Chi ; Srinivas, Sandy ; Sella, Avishay ; Schöffski, Patrick ; Scheffold, Christian ; Weitzman, Aaron L. ; Hussain, Maha. / Cabozantinib in patients with advanced prostate cancer : Results of a phase II randomized discontinuation trial. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 4. pp. 412-419.
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T2 - Results of a phase II randomized discontinuation trial

AU - Smith, David C.

AU - Smith, Matthew R.

AU - Sweeney, Christopher

AU - Elfiky, Aymen A.

AU - Logothetis, Christopher

AU - Corn, Paul G.

AU - Vogelzang, Nicholas J.

AU - Small, Eric J.

AU - Harzstark, Andrea L.

AU - Gordon, Michael S.

AU - Vaishampayan, Ulka N.

AU - Haas, Naomi B.

AU - Spira, Alexander

AU - Lara, Primo N.

AU - Lin, Chia Chi

AU - Srinivas, Sandy

AU - Sella, Avishay

AU - Schöffski, Patrick

AU - Scheffold, Christian

AU - Weitzman, Aaron L.

AU - Hussain, Maha

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N2 - 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.

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