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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Smith, DC; Daignault-Newton, S; Grivas, P; Reichert, ZR; Hussain, M; Cooney, KA; Caram, M; Alva, A; Jacobson, J; Yablon, C; Mehra, R; Escara-Wilke, J; Shelley, G; Keller, ET

Published Date

  • August 2020

Published In

Volume / Issue

  • 18 / 4

Start / End Page

  • 332 - 339.e2

PubMed ID

  • 32299729

Pubmed Central ID

  • PMC8802308

Electronic International Standard Serial Number (EISSN)

  • 1938-0682

Digital Object Identifier (DOI)

  • 10.1016/j.clgc.2019.10.019


  • eng

Conference Location

  • United States