New Antiandrogen Compounds Compared to Docetaxel for Metastatic Hormone Sensitive Prostate Cancer: Results from a Network Meta-Analysis

J Urol. 2020 Apr;203(4):751-759. doi: 10.1097/JU.0000000000000636. Epub 2019 Nov 5.

Abstract

Purpose: Docetaxel represent the standard of care in patients with metastatic, hormone sensitive prostate cancer. However, androgen receptor axis targeted therapies have also been shown to be effective. We aimed to analyze findings in randomized controlled trials investigating first-line treatment for hormone sensitive prostate cancer.

Materials and methods: We systematically reviewed the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and the PICO (Population, Intervention, Comparator, Outcomes) methodology. Outcomes of interest were overall and progression-free survival, and the rate of high grade adverse events.

Results: No treatment was superior to docetaxel in terms of overall survival. However, abiraterone (HR 0.89, 95% CI 0.76-1.05), enzalutamide (HR 0.90, 95% CI 0.69-1.19) and apalutamide (HR 0.90, 95% CI 0.67-1.22) showed nonstatistically significant lower overall mortality rates than docetaxel. Abiraterone (HR 0.71, 95% CI 0.59-0.86), enzalutamide (HR 0.61, 95% CI 0.49-0.75) and apalutamide (HR 0.74, 95% CI 0.57-0.95) also showed statistically significant lower disease progression rates than docetaxel. Furthermore, abiraterone (OR 0.83, 95% CI 0.56-1.21) showed no statistically significant lower rate of high grade adverse events compared to docetaxel. Finally, enzalutamide (OR 0.56, 95% CI 0.35-0.92) and apalutamide (OR 0.44, 95% CI 0.24-0.79) showed statistically significant lower rates of high grade adverse events compared to docetaxel.

Conclusions: Treatment with androgen receptor axis targeted therapies combined with androgen deprivation therapy in patients with hormone sensitive prostate cancer did not offer a statistically significant advantage in overall survival compared to the standard, docetaxel. However, it was associated with a lower disease progression rate. Moreover, apalutamide and enzalutamide offer a better safety profile.

Keywords: androgen; drug related side effects and adverse reactions; mortality; neoplasm metastasis; prostatic neoplasms; receptors.

MeSH terms

  • Androgen Antagonists / administration & dosage*
  • Androgen Antagonists / adverse effects
  • Androstenes / administration & dosage
  • Androstenes / adverse effects
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Benzamides
  • Disease Progression
  • Docetaxel / administration & dosage*
  • Docetaxel / adverse effects
  • Humans
  • Male
  • Network Meta-Analysis
  • Nitriles
  • Phenylthiohydantoin / administration & dosage
  • Phenylthiohydantoin / adverse effects
  • Phenylthiohydantoin / analogs & derivatives
  • Progression-Free Survival
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Randomized Controlled Trials as Topic
  • Standard of Care
  • Thiohydantoins / administration & dosage
  • Thiohydantoins / adverse effects

Substances

  • Androgen Antagonists
  • Androstenes
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Thiohydantoins
  • apalutamide
  • Docetaxel
  • Phenylthiohydantoin
  • enzalutamide
  • abiraterone