Drug-drug interaction potential among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with novel androgen receptor inhibitors

Expert Rev Anticancer Ther. 2024 May;24(5):325-333. doi: 10.1080/14737140.2024.2328778. Epub 2024 Mar 12.

Abstract

Background: Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients are often older and use concurrent medications that increase the potential for drug-drug interactions (pDDIs). This study assessed pDDI prevalence in real-world nmCRPC patients treated with apalutamide, darolutamide, or enzalutamide.

Research design and methods: Castrated prostate cancer patients without metastases prior to androgen receptor inhibitor initiation were identified retrospectively via Optum Clinformatics Data Mart claims data (8/2019-3/2021). The top 100 concomitant medications were assessed for pDDIs.

Results: Among 1,515 patients (mean age: 77 ± 8 years; mean Charlson Comorbidity Index: 3 ± 3), 340 initiated apalutamide, 112 darolutamide, and 1,063 enzalutamide. Common concomitant medication classes were cardiovascular (80%) and central nervous system (52%). Two-thirds of the patients received ≥5 concomitant medications; 30 (30/100 medications) pDDIs were identified for apalutamide and enzalutamide each and 2 (2/100 medications) for darolutamide. Most pDDIs had risk ratings of C or D, but four for apalutamide were rated X. Approximately 58% of the patients on apalutamide, 5% on darolutamide, and 54% on enzalutamide had ≥1 identified pDDI.

Conclusions: Results showed a higher frequency of pDDIs in patients receiving apalutamide and enzalutamide vs darolutamide. The impact of these could not be determined retrospectively. DDI risk should be carefully evaluated when discussing optimal therapy for patients with nmCRPC.

Keywords: androgen receptor inhibitor; claims data; drug-drug interactions; nmCRPC; polypharmacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Receptor Antagonists* / administration & dosage
  • Androgen Receptor Antagonists* / adverse effects
  • Androgen Receptor Antagonists* / pharmacology
  • Benzamides* / administration & dosage
  • Benzamides* / pharmacology
  • Drug Interactions*
  • Humans
  • Male
  • Nitriles* / administration & dosage
  • Phenylthiohydantoin* / administration & dosage
  • Phenylthiohydantoin* / adverse effects
  • Phenylthiohydantoin* / pharmacology
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyrazoles* / pharmacology
  • Retrospective Studies
  • Thiohydantoins* / administration & dosage
  • Thiohydantoins* / adverse effects
  • Thiohydantoins* / pharmacology

Substances

  • enzalutamide
  • apalutamide
  • Phenylthiohydantoin
  • Benzamides
  • darolutamide
  • Androgen Receptor Antagonists
  • Thiohydantoins
  • Nitriles
  • Pyrazoles