Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure

Hielke J. Meulenbeld, Jean P. Bleuse, Elio M. Vinci, Eric Raymond, Giordano Vitali, Armando Santoro, Luigi Dogliotti, Rossana Berardi, Federico Cappuzzo, Scott T. Tagawa, Cora N. Sternberg, Maria G. Jannuzzo, Mariangela Mariani, Anna Petroccione, Ronald De Wit

Research output: Contribution to journalArticle

Abstract

Objective: To determine the efficacy and toxicity of danusertib (formerly PHA-739358) administered i.v. over two different dosing schedules with equivalent dose intensity in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment. Patients and Methods: In this open-label, multicentre phase II trial 88 patients were randomly assigned (1:1 ratio) to receive either danusertib 330 mg/m 2 over 6 h i.v. on days 1, 8 and 15 (arm A, n = 43) or 500 mg/m 2 over 24 h i.v. on days 1 and 15 (arm B, n = 38), every 4 weeks. The primary endpoint chosen for this exploratory study was PSA response rate at 3 months. Results Sixty patients (31/43 in arm A and 29/38 in arm B) were evaluable for the primary endpoint. Median progression-free survival was 12 weeks in both arms. PSA response occurred in one patient in each arm; best overall response was stable disease in eight (18.6%) and 13 (34.2%) patients in arms A and B, respectively. Eleven out of 81 (13.6%) treated patients had stable disease for ≥6 months. Danusertib was generally well tolerated; the most common grade 3 and 4 drug-related adverse event was neutropenia which occurred in 37.2% (arm A) and 15.8% (arm B) of the patients. Conclusion Danusertib monotherapy shows minimal efficacy in patients with castration-resistant prostate cancer. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization.

Original languageEnglish
Pages (from-to)44-52
Number of pages9
JournalBJU International
Volume111
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • aurora kinase
  • aurora kinase inhibitor
  • castration-resistant prostate cancer
  • danusertib
  • PHA-739358

ASJC Scopus subject areas

  • Urology

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  • Cite this

    Meulenbeld, H. J., Bleuse, J. P., Vinci, E. M., Raymond, E., Vitali, G., Santoro, A., Dogliotti, L., Berardi, R., Cappuzzo, F., Tagawa, S. T., Sternberg, C. N., Jannuzzo, M. G., Mariani, M., Petroccione, A., & De Wit, R. (2013). Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. BJU International, 111(1), 44-52. https://doi.org/10.1111/j.1464-410X.2012.11404.x