Darolutamide Demonstrates Strong Safety Profile in mCRPC after Long-Term Analyses

Darolutamide produced a well-tolerated safety profile in patients with metastatic castration-resistant prostate cancer, according to pooled data from long-term analyses of 3 trials.

Darolutamide (Nubeqa) produced a well-tolerated safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC), according to pooled data from long-term analyses of 3 trials.1

The analysis from first author Egils Vjaters, MD, Pauls Stradiņš Clinical University Hospital, and coauthors was shared during a poster session at the 2022 ASCO Genitourinary Cancers symposium. Overall, the small study included 13 patients with mCRPC enrolled across the phase 1/2 ARADES (NCT01317641/NCT01429064), phase 1 ARAFOR (NCT01784757), and Japanese Phase 1 (NCT02363855) trials. All 13 patients had received darolutamide for more than 2 years, with a median treatment time of 38 months (range, 24-90).

The median patient age was 68 years (range, 55-81), 12 patients were White, and 1 patient was Asian. The patients were from France (n = 4), the United Kingdom (n = 3), Latvia (n = 3), Finland (n = 2), and Japan (n = 1). The median time since initial diagnosis was 32.4 months (range, 9.7-191.0).

Ten patients had normal renal function (eGFR ≥90 mL/min) at baseline and 3 patients had mild renal impairment (eGFR ≥60 to <90 mL/min). Similarly, 10 patients had normal hepatic function at baseline and 3 had mild hepatic impairment. There were 12 patients with a baseline ECOG performance status (PS) of 0, and 1 patient with a baseline PS of 1. Nine patients had a Gleason score ≥7 and the remaining 3 patients had a Gleason score of <7. The median baseline PSA was 18.1 µg/L (range, 4.6-53.6).

Initial treatment patients received for their primary tumor included chemical castration (n = 7), radiotherapy (n = 4), hormonal therapy (n = 1), and prostatectomy (n = 1). Prior and concomitant anticancer therapy patients received before the start of the study treatment included androgen-deprivation therapy (n = 13), bicalutamide (n = 10), triptorelin acetate (n = 6), goserelin acetate (n = 4), leuprorelin acetate (n= 3), cyproterone acetate (n = 3), degarelix acetate (n = 2), and abiraterone acetate (n = 1). There were no patients who had received sipuleucel-T (Provenge), docetaxel, radium-223 (Xofigo), cabazitaxel (Jevtana), or mitoxantrone.

Regarding dosing, the 8 patients from the ARAFOR study and the 1 patient from the Japanese Phase 1 trial received darolutamide at 600 mg twice daily. Among the ARADES patients, 2 were dosed at 700 mg twice daily, and 1 each received 200 mg and 300 mg twice daily, respectively.

All 13 patients experienced treatment-emergent adverse events (TEAEs). Across all reported TEAEs, regardless of whether they were categorized as drug-related, the worst severity was grade 1 or 2 for 7 patients and grade 3 for 6 patients. Six of these all-cause AEs were serious AEs and 1 led to discontinuation of darolutamide. According to the study authors, the discontinuation stemmed from a new locally advanced rectal adenocarcinoma that was not related darolutamide.

Across all of the TEAEs, there were 7 that occurred in more than 2 patients: diarrhea (n = 5), abdominal pain (n = 4), nausea (n = 4), arthralgia (n = 3), fatigue (n = 3), hematuria (n = 3), and influenza (n = 3). All of these cases were grade 1/2 except for 1 case of grade 3 nausea and 1 case of grade 3 hematuria.

There were 5 patients who experienced TEAEs considered to be drug-related. All of these drug-related AEs were grade 1, and none were serious or led to discontinuing darolutamide.

Darolutamide was approved by the FDA in 2019 for the treatment of patients with non-metastatic CRPC. According to the study authors, long-term follow-up for darolutamide in this nonmetastatic setting has consistently shown similar rates of AE-related discontinuation between darolutamide and placebo. With their study, Vjaters et al aimed to show that this positive safety/tolerability profile for darolutamide also extended to the metastatic setting.


  1. Vjaters E, Fizazi K, James ND, et al. Long-term safety of darolutamide in patients with metastatic castration-resistant prostate cancer. J Clin Oncol 40, 2022 (suppl 6; abstr 90) doi: 10.1200/JCO.2022.40.6_suppl.090