Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer

David C. Smith*, Stephanie Daignault-Newton, Petros Grivas, Zachery R. Reichert, Maha Hussain, Kathleen A. Cooney, Megan Caram, Ajjai Alva, Jon Jacobson, Corrie Yablon, Rohit Mehra, June Escara-Wilke, Greg Shelley, Evan T. Keller

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: Cabozantinib is active in advanced prostate cancer with improvement on bone scans in men on phase II trials. This trial evaluated the efficacy and changes in bone lesions in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib. Patients and Methods: Eligible patients with mCRPC involving bone underwent biopsy of a bone lesion followed by cabozantinib starting at 60 mg daily and continuing until progression or intolerable toxicity. The primary study endpoint was progression-free survival at 12 weeks. The bone lesion was rebiopsied at 6 weeks. Expression of CMET, phospho-CMET, and VEGFR2 was assayed by immunohistochemistry. Serum was obtained at baseline, and at 3, 6, and 12 weeks and assayed for bone remodeling markers. Results: A total of 25 patients were enrolled: 22 were evaluable, and 3 were excluded before receiving cabozantinib. At 12 weeks, 17 (77%) of 22 patients had stable disease or better. The median time on treatment was 24 weeks (range, 3-112 weeks). The overall median progression-free survival was 43.7 weeks (95% confidence interval, 23.7-97.0 weeks). Eight (36%) of 22 patients had markedly reduced uptake on bone scan. Patients with significant response on bone scan had higher bone morphogenic protein-2 levels at baseline, stable N-telopeptides levels, increased vascular endothelial growth factor receptor 2 expression, and a trend towards increased phospho-CMET while on cabozantinib compared with patients with stable disease. Conclusions: Cabozantinib is active in men with mCRPC, inducing significant changes on bone scan in one-third of patients with changes in markers of bone formation and the tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)332-339.e2
JournalClinical Genitourinary Cancer
Volume18
Issue number4
DOIs
StatePublished - Aug 2020
Externally publishedYes

Keywords

  • Markers of bone metabolism

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint Dive into the research topics of 'Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer'. Together they form a unique fingerprint.

  • Cite this

    Smith, D. C., Daignault-Newton, S., Grivas, P., Reichert, Z. R., Hussain, M., Cooney, K. A., Caram, M., Alva, A., Jacobson, J., Yablon, C., Mehra, R., Escara-Wilke, J., Shelley, G., & Keller, E. T. (2020). Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. Clinical Genitourinary Cancer, 18(4), 332-339.e2. https://doi.org/10.1016/j.clgc.2019.10.019