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Long-term data show darolutamide is safe for patients with metastatic CRPC


A pooled long-term safety analysis from 3 trials of patients with metastatic castration-resistant prostate cancer (mCRPC) showed that darolutamide (Nubeqa) was well tolerated overall and had comparable safety and tolerability to previously reported data for the androgen receptor inhibitor.1

Egils Vjaters, MD

Egils Vjaters, MD

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

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