ASCO GU 2023: Darolutamide plus ADT Versus ADT in Metastatic Hormone-Sensitive Prostate Cancer: Open-Label Single-Arm Study with an External Control Arm (ARASEC)

( The 2023 GU ASCO annual meeting included a session on trials in progress for prostate cancer, featuring a presentation by Dr. Neal Shore discussing the trial design of ARASEC, an open-label single-arm study with an external control of darolutamide plus ADT versus ADT in metastatic hormone-sensitive prostate cancer. Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor. In the phase 3 ARAMIS study (NCT02200614)1 in nonmetastatic castration-resistant prostate cancer, darolutamide + ADT significantly improved metastasis-free survival and overall survival (OS) vs placebo + ADT, with a favorable tolerability and safety profile. In the phase 3 ARASENS study (NCT02799602)2 in metastatic hormone-sensitive prostate cancer, darolutamide + ADT + docetaxel significantly reduced the risk of death by 32.5% vs ADT + docetaxel (HR 0.68; 95% CI 0.57–0.80), with no additional adverse events. Darolutamide + ADT vs ADT alone in patients with metastatic hormone-sensitive prostate cancer is being evaluated in the ongoing, global (excluding the United States), phase 3 ARANOTE study (NCT04736199). The phase 2 ARASEC study (NCT05059236) will complement ARANOTE by evaluating darolutamide + ADT in US patients with metastatic hormone-sensitive prostate cancer. Given that ADT alone is no longer an acceptable comparator in the United States, an external control arm will be derived from a historical study.

To participate in ARASEC, patients must have confirmed adenocarcinoma of the prostate, metastatic disease on conventional imaging for which they have not received prior systemic therapy, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients will receive darolutamide 600 mg twice daily + ADT (luteinizing hormone-releasing hormone agonist/antagonist or orchiectomy). ADT can be started ≤4 months before darolutamide, and there must be no evidence of progression on ADT before darolutamide initiation. The external control arm will be derived from 394 patients with metastatic hormone-sensitive prostate cancer treated with ADT alone in CHAARTED (NCT00309985).3 The trail design for ARASEC is as follows:


Patients in the active and control arms will be matched 1:1 on baseline characteristics such as age, ECOG PS, CHAARTED-defined extent of disease, prior therapy, and Gleason score. The propensity score (ie, the assessed probability that a patient is allocated to the darolutamide + ADT arm based on baseline profile) will be used to address bias in estimating differential effects, by matching patients with scores within a narrow window across the cohorts. The primary endpoint for ARASEC is progression-free survival, defined as the time from enrollment to PSA progression, radiologic or symptomatic progression, clinical deterioration, or death, whichever occurs first, as defined in CHAARTED. Secondary endpoints are:

  • OS
  • Radiographic progression-free survival
  • Time to castration-resistant prostate cancer
  • 6-month PSA response (<0.2 ng/mL)
  • Safety

The study will continue until either the event count threshold triggering the primary endpoint analysis (161 progression-free survival events) has been met or all patients have been followed for ≥2 years after enrollment, whichever occurs later. Dr. Shore concluded his presentation by highlighting that ARASEC is enrolling, with the first patient enrolled in November 2021. As of January 2023, 121 patients have been enrolled. The target total enrollment is 200 patients at 30 sites:


Clinical trial information: NCT05059236

Presented by: Neal D. Shore, MD, FACS, Carolina Urologic Research Center, Myrtle Beach, SC

Co-Authors: Mark A. Preston, Justin R Gregg, Simpa Samuel Salami, Ashley Ross, Amanda Bruno, Shankar Srinivasan, Niculae Constantinovici, Jorge A. Ortiz, Patrick Adorjan, Frank Verholen, Rana R. McKay

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 American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2023, February 16, 2023 – February 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.
  2. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142.
  3. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.