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

Publication ,  Journal Article
Smith, DC; Daignault-Newton, S; Grivas, P; Reichert, ZR; Hussain, M; Cooney, KA; Caram, M; Alva, A; Jacobson, J; Yablon, C; Mehra, R ...
Published in: Clin Genitourin Cancer
August 2020

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.

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Published In

Clin Genitourin Cancer

DOI

EISSN

1938-0682

Publication Date

August 2020

Volume

18

Issue

4

Start / End Page

332 / 339.e2

Location

United States

Related Subject Headings

  • Survival Rate
  • Pyridines
  • Prostatic Neoplasms, Castration-Resistant
  • Prognosis
  • Oncology & Carcinogenesis
  • Non-Randomized Controlled Trials as Topic
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans
 

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Smith, D. C., Daignault-Newton, S., Grivas, P., Reichert, Z. R., Hussain, M., Cooney, K. A., … Keller, E. T. (2020). Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. Clin Genitourin Cancer, 18(4), 332-339.e2. https://doi.org/10.1016/j.clgc.2019.10.019
Smith, David C., Stephanie Daignault-Newton, Petros Grivas, Zachery R. Reichert, Maha Hussain, Kathleen A. Cooney, Megan Caram, et al. “Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer.Clin Genitourin Cancer 18, no. 4 (August 2020): 332-339.e2. https://doi.org/10.1016/j.clgc.2019.10.019.
Smith DC, Daignault-Newton S, Grivas P, Reichert ZR, Hussain M, Cooney KA, et al. Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. Clin Genitourin Cancer. 2020 Aug;18(4):332-339.e2.
Smith, David C., et al. “Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer.Clin Genitourin Cancer, vol. 18, no. 4, Aug. 2020, pp. 332-339.e2. Pubmed, doi:10.1016/j.clgc.2019.10.019.
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. Efficacy and Effect of Cabozantinib on Bone Metastases in Treatment-naive Castration-resistant Prostate Cancer. Clin Genitourin Cancer. 2020 Aug;18(4):332-339.e2.
Journal cover image

Published In

Clin Genitourin Cancer

DOI

EISSN

1938-0682

Publication Date

August 2020

Volume

18

Issue

4

Start / End Page

332 / 339.e2

Location

United States

Related Subject Headings

  • Survival Rate
  • Pyridines
  • Prostatic Neoplasms, Castration-Resistant
  • Prognosis
  • Oncology & Carcinogenesis
  • Non-Randomized Controlled Trials as Topic
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Humans