Androgen receptor variant 7 (AR-V7) in sequencing therapeutic agents for castratrion resistant prostate cancer: A critical review

Medicine (Baltimore). 2019 May;98(19):e15608. doi: 10.1097/MD.0000000000015608.

Abstract

Background: androgen receptor variant 7 (AR-V7) has been suggested as potential marker for treatment selection in men with metastatic castration-resistant prostate cancer (mCRPC). The aim of the present review is to critically analyze: frequency of the AR-V7 expression in mCRPC cases-impact of AR-V7 expression on abiraterone, enzalutamide, and taxane therapy.

Methods: we searched in the Medline and Cochrane Library database from the literature of the past 10 years. We critically evaluated the level of evidence according to the European Association of Urology (EAU) guidelines.

Results: 12 clinical trials were selected. The determination of AR-V7 in peripheral blood using circulating tumor cells mRNA seems to be the preferred method. At baseline, the mean percentage of cases with AR-V7 positivity was 18.3% (range 17.8%-28.8%). All data on mCRPC submitted to enzalutamide or abiraterone reported a significantly (P <.05) lower clinical progression-free survival (CPFS) and overall survival (OS) in AR-V7+ than AR-V7- cases (CPFS hazard ratio [HR]: 2.3; 95% CI 1.1-4.9; OS HR: 3.0; 95% CI 1.4-6.3). In mCRPC cases submitted to chemotherapies data are not homogeneous and some studies showed no association between CPFS or OS and AR-V7 status (OS HR 1.6; 95% CI 0.6-4.4; P = .40).

Conclusions: the suggestion is that taxane therapy is more efficacious than abiraterone or enzalutamide for men with AR-V7+ CRPC. On the contrary, clinical outcomes did not seem to differ significantly on the basis of the type of therapy used among AR-V7- cases.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Androstenes / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Biomarkers, Tumor / genetics
  • Bridged-Ring Compounds / therapeutic use
  • Drug Resistance, Neoplasm / genetics
  • Genetic Variation
  • Humans
  • Male
  • Nitriles
  • Phenylthiohydantoin / analogs & derivatives
  • Phenylthiohydantoin / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Receptors, Androgen / genetics*
  • Taxoids / therapeutic use

Substances

  • AR protein, human
  • Androstenes
  • Antineoplastic Agents
  • Benzamides
  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • Nitriles
  • Receptors, Androgen
  • Taxoids
  • taxane
  • Phenylthiohydantoin
  • enzalutamide
  • abiraterone