SESAUA 2024: Darolutamide, Enzalutamide, and Apalutamide for Non-Metastatic Castration-Resistance Prostate Cancer Patients in the United States (DEAR): Comparative Real-World Evidence

( The 2024 American Urological Association (AUA) Southeastern Section annual meeting held in Austin, TX between March 20th and 23rd hosted a prostate cancer poster session. Dr. Zachary Klaassen presented the results of a real-world analysis (DEAR) comparing darolutamide, enzalutamide, and apalutamide for non-metastatic castrate-resistant prostate cancer (nmCRPC) patients in the United States.

Currently, there are three androgen receptor pathway inhibitors (darolutamide, enzalutamide, and apalutamide) approved for the treatment of patients with nmCRPC.1-3 To date, there are no head-to-head trials comparing these agents in the nmCRPC setting. As such, real-world comparative evidence is needed to inform practice in this setting. DEAR is the first study to compare real-world utilization, outcomes, and occurrence of adverse events between these agents in men with nmCRPC. 

In this study, patients were classified into one of three treatment cohorts, based on the androgen receptor pathway inhibitor first prescribed at the nmCRPC stage:


The study inclusion criteria were as follows:

  • Men aged ≥18 years at the index date
  • Diagnosed with nmCRPC before their first ever androgen receptor treatment initiation
  • Minimum 6-months baseline period and a ≥6-month follow-up period, unless the patient died earlier

The study exclusion criteria were as follows:

  • Evidence of metastatic disease before or 30 days after the index date
  • Prior history of other primary cancers, except non-melanoma skin cancer, in the 5 years before the index date
  • Prior use of a novel antihormonal agent (darolutamide, enzalutamide, apalutamide, or abiraterone acetate)
  • Initiation of multiple androgen receptor pathway inhibitors recorded on the same date
  • Evidence of inclusion in clinical trials during the study period

For each androgen receptor pathway inhibitor cohort, the overall proportion of patients who discontinued initial treatment and who progressed to mCRPC during the study, the reasons for discontinuation, and the proportion of patients with adverse events were described. Kaplan-Meier estimates of time to discontinuation of initial treatment and time to progression were calculated. Cox proportional hazards models were used to compare time to treatment discontinuation and time to progression to mCRPC between treatment cohorts, before and after adjusting for baseline factors, which included: age, race, insurance coverage, index year, PSA, PSA doubling time, time from nmCRPC diagnosis to index date, and Gleason score.

The observed baseline characteristics and duration of follow-up were similar across the three treatment cohorts:


Compared to nmCRPC patients receiving enzalutamide and apalutamide, those receiving darolutamide had 27.4% and 39.1% lower rates of discontinuation of initial androgen receptor pathway inhibitor treatment, respectively.


Summarized below are the reasons for treatment discontinuation, most commonly adverse events-related across all three treatment groups:


Compared to nmCRPC patients receiving enzalutamide and apalutamide, those receiving darolutamide had 40.6% and 35.3% lower rates of progression to mCRPC, respectively.


Patients receiving darolutamide had a lower incidence of adverse events, compared with those receiving enzalutamide or apalutamide.


Dr. Klaassen noted the following limitations to this analysis:

  • While the analysis adjusts for observed differences in baseline characteristics between the 3 treatment cohorts, unobserved confounding factors may also influence treatment duration and clinical outcomes in the absence of randomization.
  • Other limitations may include the ability to generalize results to other patient populations, although limitations related to the mismeasurement or missingness of study variables would affect results only to the extent that cohorts were affected differently

He concluded that:

  • This is the first real-world analysis assessing treatment discontinuation and underlying reasons for discontinuation, progression to mCRPC, and incidence of adverse events for the 3 androgen receptor pathway inhibitors approved for nmCRPC (darolutamide, enzalutamide, and apalutamide).
  • Observed baseline characteristics and median duration of follow-up (~2 years) were similar across the 3 treatment cohorts
  • Results suggest that treatment with darolutamide was associated with lower rates of treatment discontinuation and progression to mCRPC, compared with enzalutamide and apalutamide
  • In addition, a lower proportion of patients had adverse events on darolutamide, compared with enzalutamide and apalutamide
  • Future studies are needed to confirm these results in other populations or using other data sources 

Presented by: Zachary Klaassen, MD, MSc, Associate Professor, Department of Urology, Wellstar MCG Health, Augusta, GA

Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 Southeastern Section of the American Urological Association (SESAUA) Annual Meeting, Austin, TX, Wed, Mar 20 – Sat, Mar 23, 2024. 


  1. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.
  2. Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474.
  3. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med 2018;378(15):1408-1418.