Enzalutamide versus abiraterone acetate in the development of new-onset or worsening type 2 diabetes mellitus in patients with metastatic castration-resistant prostate cancer: EVADE study

World J Urol. 2024 Oct 18;42(1):584. doi: 10.1007/s00345-024-05280-y.

Abstract

Purpose: To determine new-onset or worsening T2DM risk in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone acetate (AA) vs. enzalutamide (ENZA) in England.

Methods: Records of patients on AA and/or ENZA (2015-2021) were analysed retrospectively from UK- or England-wide databases and data sets. The primary endpoint was new-onset or worsening T2DM, analysed using a Cox model.

Results: Of 1382 patients, 84 (6.1%) met the primary endpoint; 42 of 826 patients (5.1%) received ENZA and 42 of 556 patients (7.6%) received AA. Among patients without baseline T2DM (n = 1049), 50 developed new-onset T2DM: 24 (3.9%) on ENZA and 26 (5.9%) on AA. Among patients with baseline T2DM (n = 333), 34 (10.2%) had worsening T2DM: 18 (8.3%) on ENZA and 16 (13.8%) on AA. Patients on ENZA had longer median follow-up (445 vs. 408 days) and treatment duration (164 vs. 139 days) than those on AA, who were also more likely to have new-onset or worsening T2DM than those on ENZA (HR: 1.8; 95% CI: 1.4-2.7; P = 0.0101). The number needed to harm for an additional patient to experience new-onset or worsening T2DM when receiving AA instead of ENZA was 40 overall, 50 in patients without baseline T2DM, and 18 in patients with baseline T2DM.

Conclusion: Patients with mCRPC receiving AA were more likely to experience new-onset or worsening T2DM than those on ENZA, despite having a shorter treatment duration. Further research is required to substantiate these findings in earlier disease settings with longer treatment duration.

Keywords: Abiraterone; Androgen receptor pathway inhibitor; Enzalutamide; Metastatic castration-resistant prostate cancer; Type 2 diabetes mellitus.

Publication types

  • Comparative Study

MeSH terms

  • Abiraterone Acetate* / therapeutic use
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Benzamides* / therapeutic use
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Disease Progression*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Nitriles* / therapeutic use
  • Phenylthiohydantoin* / analogs & derivatives
  • Phenylthiohydantoin* / therapeutic use
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Retrospective Studies

Substances

  • enzalutamide
  • Phenylthiohydantoin
  • Abiraterone Acetate
  • Benzamides
  • Nitriles
  • Antineoplastic Agents