ASCO GU 2023: Real-World Use of Darolutamide, Enzalutamide, and Apalutamide for Non-Metastatic Castration-Resistant Prostate Cancer (DEAR)

( The 2023 GU ASCO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Daniel George discussing results from DEAR, a real-world use of darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer.

Second-generation androgen receptor inhibitors are the preferred treatment for patients in this disease space. In this setting, an important therapeutic goal is to minimize adverse events and prolong time on androgen receptor inhibitor treatment. This is the first study to assess real-world utilization and outcomes of all currently available androgen receptor inhibitors (darolutamide, enzalutamide, and apalutamide) in patients with non-metastatic castration-resistant prostate cancer.

DEAR (NCT05362149) is a retrospective observational chart review using electronic medical records from the Precision Point Specialty network of US urology practices. Eligibility criteria included:

  • Non-metastatic castration-resistant prostate cancer diagnosis
  • No previous treatment with a novel hormonal agent
  • Androgen receptor inhibitor treatment initiation for the first time from August 1, 2019 to March 31 2022


Patients were classified into 3 cohorts based on the first prescribed androgen receptor inhibitor in the non-metastatic castration-resistant prostate cancer stage. At the GU ASCO 2023 meeting, Dr. George and colleagues present an interim report including the primary composite endpoint (discontinued treatment/metastasis), defined as a proportion of patients who discontinued initial androgen receptor inhibitor treatment or progressed to metastasis, as well as key secondary endpoints including time to discontinued treatment/metastasis and underlying reasons.

In total, 828 patients were included (n = 340 darolutamide, n = 367 enzalutamide, n = 121 apalutamide). The proportion of patients starting treatment with darolutamide increased during the study period relative to enzalutamide or apalutamide, which declined or remained stable, respectively:

ARI treatment.jpg

The median age (darolutamide 80, enzalutamide 79, and apalutamide 80 years), White race (darolutamide 67%, enzalutamide 67%, and apalutamide 74%) and median PSA doubling time (darolutamide 6.5, enzalutamide 6.4, and apalutamide 7.4 months) at baseline were similar in the darolutamide/ enzalutamide/apalutamide cohorts. Additionally, the median length of follow-up was similar:

Fewer patients had a discontinued treatment/metastasis event during the study in the darolutamide cohort (37%), compared with enzalutamide or apalutamide (enzalutamide 51%, apalutamide 51%); this trend was seen within 6 to 24 months after androgen receptor inhibitor initiation:


The median time to discontinued treatment/metastasis was not reached for darolutamide (95% CI 30.1, NR), 23.1 (95% CI 18.2, 26.4) months for enzalutamide, and 20.5 (95% CI 12.3, 27.2) months for apalutamide:

The most common reasons for discontinued treatment/metastasis was adverse events (darolutamide 9.7%, enzalutamide 14.4%, and apalutamide 15.7%):

discontinuation reasons.jpg

Dr. George concluded his presentation discussing results from DEAR, a real-world use of darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer with the following concluding messages:

  • This real-world study in the US shows that, despite similar baseline characteristics, fewer non-metastatic castration-resistant prostate cancer patients treated with darolutamide had discontinued/metastasis (especially due to adverse events/metastasis) versus enzalutamide and apalutamide, and the time to this event was longer in the darolutamide cohort
  • These findings may be attributed to darolutamide being a structurally distinct androgen receptor inhibitor with low potential for blood–brain barrier penetration
  • This real-world evidence study reinforces the favorable safety profile of darolutamide in the ARAMIS study [1]. It further demonstrates the importance of treatment tolerability and the potential for longer treatment duration with darolutamide compared to enzalutamide and apalutamide, which may in turn improve treatment outcomes

Presented by: Daniel J. George, MD, Professor, Duke Cancer Institute Center for Prostate and Urologic Cancers, Durham, NC

Co-Authors: Nasreen Khan, Niculae Constantinovici, Javeed Khan, Guifang Chen, Julie Xu, Jorge A. Ortiz, Alicia K. Morgans 

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, Thurs, Feb 16 – Sat, Feb 18, 2023.


  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.