Prognostic Parameters for Response to Enzalutamide After Docetaxel and Abiraterone Treatment in Metastatic Castration-Resistant Prostate Cancer Patients: a Possible Time Relation

Sushil K. Badrising, Vincent van der Noort, Alfons J. M. van den Eertwegh, Paul Hamberg, Inge M. van Oort, Hendrik P. van den Berg, Maartje Los, Maureen J. B. Aarts, Jules L. L. M. Coenen, Hans Gelderblom, Igle J. de Jong, Emile D. Kerver, Suzan Vrijaldenhoven, Theo van Voorthuizen, Fabienne Warmerdam, John B. Haanen, Andries M. Bergman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Metastatic castration-resistant prostate cancer (mCRPC) is a prevalent and incurable disease, associated with high morbidity and mortality [1]. In recent
years multiple drugs have become available that showed an increased quality of life and overall survival (OS) of mCRPC patients. Abiraterone acetate in combination with prednisone (AA) and Enzalutamide (Enz) both target the androgen receptor and both have proven efficacy in patients with mCRPC [2–5]. Enz inhibits Androgen-Receptor (AR) signaling through inhibition of androgen binding to the AR, reducing the efficiency of the AR complex nuclear translocation, preventing the AR complex from binding to response elements in the DNA and recruitment of its coactivators [3], while AA inhibits
the synthesis of testosterone [6]. Several retrospective studies evaluated the efficacy of Enz in mCRPC patients previously treated with Docetaxel (Doc) and
AA. The rate of PSA responses (50% PSA decline) varied between 12.8% and 39.1% [7–13], OS and Progression Free Survival (PFS) varied between
4.8–8.5 months [7,9,11] and between 2.9–4.0 months [7–9,12], respectively. The reported PSA response rates, OS and PFS of Enz after Doc and AA treatment were all lower than the 54%, 18.4 months and 8.3 months, respectively, reported in mCRPC patients previously treated with Doc only [3]. These results
suggest a significant clinical cross-resistance, however, a proportion of patients treated with Enz previously treated with Doc and AA did have a PSA
response. Here we report the characteristics of these patients. This information might be of value for optimal sequencing of treatment options for mCRPC patients.
Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalProstate
Volume76
Issue number1
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • prostate cancer
  • enzalutamide
  • abiraterone
  • docetaxel
  • cross-resistance
  • AR plasticity

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