Expression of AR-V7 in Circulating Tumour Cells Does Not Preclude Response to Next Generation Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer

Eur Urol. 2017 Jan;71(1):1-3. doi: 10.1016/j.eururo.2016.07.021. Epub 2016 Jul 26.

Abstract

The androgen receptor splice variant AR-V7 has recently been discussed as a predictive biomarker for nonresponse to next-generation androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer. However, we recently identified one patient showing a response from abiraterone despite expression of AR-V7 in his circulating tumour cells (CTC). Therefore, we precisely assessed the response in a cohort of 21 AR-V7 positive castration-resistant prostate cancer patients who had received therapy with abiraterone or enzalutamide. We detected a subgroup of six AR-V7 positive patients showing benefit from either abiraterone or enzalutamide. Their progression free survival was 26 d (censored) to 188 d. Four patients displayed a prostate-specific antigen decrease of >50%. When analysing prior therapies, we noticed that only one of the six patients had received next-generation ADT prior to CTC collection. As a result, we conclude that AR-V7 status in CTC cannot entirely predict nonresponse to next generation ADT and AR-V7-positive patients should not be systematically denied abiraterone or enzalutamide treatment, especially as effective alternative treatment options are still limited.

Patient summary: A subgroup of patients can benefit from abiraterone and/or enzalutamide despite detection of AR-V7 splice variants in their circulating tumour cells.

Keywords: AR-V7; Abiraterone; Androgen receptor splice variant; Castration resistant prostate cancer; Enzalutamide.

MeSH terms

  • Androgen Receptor Antagonists / therapeutic use*
  • Androstenes / therapeutic use
  • Benzamides
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology
  • Humans
  • Male
  • Neoplastic Cells, Circulating / drug effects
  • Neoplastic Cells, Circulating / metabolism*
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / metabolism*
  • Prostatic Neoplasms, Castration-Resistant / therapy
  • Protein Isoforms / biosynthesis
  • Receptors, Androgen / biosynthesis*
  • Receptors, Androgen / metabolism
  • Retrospective Studies

Substances

  • AR protein, human
  • Androgen Receptor Antagonists
  • Androstenes
  • Benzamides
  • Nitriles
  • Protein Isoforms
  • Receptors, Androgen
  • Phenylthiohydantoin
  • enzalutamide
  • abiraterone