EAU 2021: Clinical Benefit and Safety Profile of Darolutamide in Patients Who Crossed over to Darolutamide from Placebo During the Open-Label Period of the Phase 3 ARAMIS Study

(UroToday.com) Darolutamide (DARO) is a structurally distinct androgen receptor inhibitor (ARI) that has been demonstrated to significantly prolong metastasis-free survival and overall survival in the ARAMIS trial.1

DARO significantly prolonged metastasis-free survival (MFS) and overall survival (OS) vs placebo (PBO) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in ARAMIS. DARO has a favorable safety profile, showing ≤2% difference between DARO and PBO for most adverse events (AEs) of interest associated with androgen receptor inhibitors (falls, fractures, rash, mental impairment, and hypertension). Fatigue was the only AE with >10% incidence in the DARO arm (13.2% vs 8.3% in PBO arm). After unblinding of ARAMIS (30 Nov 2018), 170 patients (pts) receiving PBO crossed over (CO) to open-label (OL) DARO.

In this abstract, the authors present the clinical benefit and safety in these CO pts. For PBO to DARO CO pts at final analysis (15 Nov 2019), PSA outcomes were used to assess clinical benefit because the treatment duration was not long enough to assess MFS or OS. The last outcome measurement before CO from PBO to DARO was the CO baseline value. AEs during the double-blind (DB) and OL periods were compared with the CO period for the same observation time, consistent with the median treatment duration in CO pts. Each site’s ethics committee approved the study.

Full demographics are below:


PBO to DARO CO pts had higher median PSA values (19.80 vs 7.06 ng/mL) and poorer performance status (Eastern Cooperative Oncology Group performance status ≥1 in 31% vs 25%) at the start of DARO treatment compared with study entry. Median treatment duration for CO pts was 11 months. At any time after CO, 85% of CO pts had a PSA50 response. This is seen in the waterfall plot below:


At 16 weeks after CO, 51% had PSA90 response – summarized below:


Compared with the DARO DB period during 11 months of treatment, DARO CO pts had similar or lower rates of any AEs (75.8% vs 70.0%), serious AEs (14.8% vs 15.3%), and AEs leading to study drug discontinuation (5.9% vs 4.7%) (Table below). Most AEs of interest had a lower incidence in CO pts compared with the DB period.


Based on the above results, the authors conclude that although the OS and MFS results substantiate the clear benefit of early treatment with DARO, there was also consistent safety and potential clinical benefits for pts who received DARO following CO from PBO in ARAMIS.

Presented by: Susan Feyerabend, Studienpraxis Urologie, Nürtingen, Germany.

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.


  1. Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. doi: 10.1056/NEJMoa2001342. PMID: 32905676.