A Phase 2 Trial of Abiraterone Followed by Randomization to Addition of Dasatinib or Sunitinib in Men With Metastatic Castration-Resistant Prostate Cancer

Nicholas Spetsieris, Myrto Boukovala, Justin A. Weldon, Alexandros Tsikkinis, Anh Hoang, Ana Aparicio, Shi Ming Tu, John C. Araujo, Amado J. Zurita, Paul G. Corn, Lance Pagliaro, Jeri Kim, Jennifer Wang, Sumit K. Subudhi, Nizar M. Tannir, Christopher J. Logothetis, Patricia Troncoso, Xuemei Wang, Sijin Wen, Eleni Efstathiou

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Resistance to novel androgen signaling inhibition and metastatic castration-resistant prostate cancer (mCRPC) progression is likely dependent on tumor microenvironment interactions. The Src pathway and neoangiogenesis have been implicated in prostate cancer progression. We studied the effect of adding the targeted agents dasatinib and sunitinib to abiraterone acetate (AA) in men with mCRPC. Patients and Methods: In this open-label randomized phase 2 study, mCRPC patients received AA. At resistance to AA, they were randomized 1:1 to combination with dasatinib or sunitinib. At second progression, patients crossed over. The primary end point was time to treatment failure (TTF), defined as time to progression or death. Secondary end points included overall survival and safety. Results: From March 2011 to February 2015, a total of 179 patients were enrolled and 132 subsequently randomized. Median TTF was 5.7 months in the dasatinib group and 5.5 months in the sunitinib group. There was no difference between the two groups in terms of TTF (hazard ratio, 0.85; 95% confidence interval, 0.59-1.22). Median overall survival from study entry was 26.3 months in the dasatinib group and 27.7 months in the sunitinib group (hazard ratio, 1.02; 95% confidence interval, 0.71-1.47). Grade 3 or higher adverse events related to study medication were more frequent with sunitinib (n = 44, 46%) compared to dasatinib (n = 26, 24%). At data cutoff, 7 patients were experiencing a continuous response to AA, with a median duration of treatment of 5.7 years. Conclusion: There is no difference in overall survival and TTF between dasatinib and sunitinib combined with abiraterone in the treatment of patients with bone mCRPC.

Original languageEnglish (US)
Pages (from-to)22-31.e5
JournalClinical Genitourinary Cancer
Volume19
Issue number1
DOIs
StatePublished - Feb 2021

Keywords

  • Androgen-signaling inhibition
  • Neoangiogenesis
  • Src pathway
  • Targeted agents
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Urology

MD Anderson CCSG core facilities

  • Biostatistics

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