Long-Term Tolerability Reported With Darolutamide Use in Patients With Nonmetastatic CRPC


Approximately 30% of patients remained on treatment with darolutamide for over 4 years, according to a long-term safety and tolerability updated from the ARAMIS rollover study.

Neal D. Shore, MD

Neal D. Shore, MD

After over 4 years of follow-up, approximately 30% of patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) who were enrolled in the ARAMIS rollover study (NCT04464226) had remained on treatment with darolutamide (Nubeqa). According to investigators who presented the findings, these results suggest that this treatment delivers a long-term clinical benefit.

The findings were presented at the 2023 Genitourinary Cancers Symposium by Neal D. Shore, MD, FACS, the director of the Carolina Urologic Research Center, Atlantic Urology Clinics in Myrtle Beach, South Carolina.1

Darolutamide was approved by the FDA in 2019 for the treatment of nmCRPC based on findings from the phase 3 ARAMIS trial (NCT02200614), a double-blind (DB), randomized, multicenter study with an open-label (OL) rollover study (ROS) (NCT04464226).

In the original ARAMIS study, darolutamide was found to significantly improve metastasis-free survival and reduce the risk of death vs placebo, with a permanent discontinuation due to adverse events (AEs) that was low and similar between the darolutamide group (8.9%) and placebo group (8.7%).2,3

“After the primary analysis, the study was unblinded. And patients in both treatment groups who had no evidence of progression were permitted to continue on darolutamide plus [androgen deprivation therapy] until the final analysis of overall survival. At the final analysis, darolutamide significantly reduced the risk of death by 31% compared with placebo. Patients who still had no evidence of metastases and who were benefiting clinically could choose to continue to receive darolutamide in the ARAMIS rollover study,” Shore explained in his presentation.

Of the 954 patients who started treatment on darolutamide on randomization, 294 (31%) entered the ROS. Median treatment duration was 1.5 years for patients in the DB period (range, 0.0-4.0); 2.1 years for patients in the DB and OL periods (range, 0.0-4.9); and 2.8 years for patients in DB, OL, and ROS periods (range, 0.0-6.8). By the data cut-off date of January 31, 2023, 30% of patients had received darolutamide for at least 4 years, and 24% of patients were still receiving darolutamide, according to the poster presented at the meeting.

Incidence of treatment-related AEs (TEAEs) increased slightly over time, “as expected with longer observation time,” the investigators noted. In total, 85.7%, 89.8%, and 91.5% of patients in the DB, DB and OL, and DB/OL/ROS periods, respectively, experienced an any-grade TEAE. In addition, 26.3%, 31.8%, and 35.5% of patients in the DB, DB and OL, and DB/OL/ROS periods, respectively, experienced a grade 3/4 TEAE. Further, 26.1%, 32.1%, and 38.5% of patients, respectively, experienced a serious TEAE, and 8.9%, 10.5%, and 12.9% of patients experienced a TEAE leading to treatment discontinuation. The investigators did not identify any new safety concerns in patients who entered the ROS.

“These findings support long-term use of darolutamide in patients with nmCRPC,” Shore concluded.


1. Shore ND, de Almeida Luz M, Ulys A, et al. Long-term safety and tolerability of darolutamide and duration of treatment in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) from the ARAMIS Rollover Study. Presented at: 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA. Abstract 147

2. Fizazi K, Shore N, Tammela TL. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246. doi:10.1056/NEJMoa1815671

3. Fizazi K, Shore N, Tammela TL. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. doi:10.1056/NEJMoa2001342

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