Darolutamide Yields Positive Safety Data in mCRPC


Patients with metastatic castration-resistant prostate cancer were observed to have a tolerable safety profile when treated with darolutamide.

Daralutamide (Nubeqa), and androgen receptor inhibitor, was observed to have tolerable and comparable safety data to previous results for patients with metastatic castration-resistant prostate cancer, according to a pooled long-term safety analysis presented at teh 2022 Genitourinary Cancers Symposium.

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.


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

Related Videos
Cretostimogene grenadenorepvec’s efficacy compares favorably with the current nonsurgical standards of care in high-risk, Bacillus Calmette Guerin–unresponsive non-muscle invasive bladder cancer.
Artificial intelligence models may be “seamlessly incorporated” into clinical workflow in the management of prostate cancer, says Eric Li, MD.
Robust genetic testing guidelines in the prostate cancer space must be supported by strong clinical research before they can be properly implemented, says William J. Catalona, MD.
Treatment with tisotumab vedotin may be a standard of care in second- or third-line recurrent or metastatic cervical cancer, says Brian Slomovitz, MD, MS, FACOG.
Future analyses will look at durvalumab/olaparib for endometrial cancer populations with TP53 and POLE alterations, as well as those with estrogen receptor and progesterone receptor positivity.
Patients with mismatch repair proficient, newly diagnosed, advanced or recurrent endometrial cancer may have enhanced benefit with the addition of olaparib to durvalumab.
Financial constraints and a lack of education among some patients and providers must be addressed to improve the real-world use of certain prostate cancer therapies, says Neeraj Agarwal, MD.
Novel anti-PSMA monoclonal antibody rosopatamab is capable of carrying a bigger payload of radiation particles, which may potentially reduce doses for patients with prostate cancer, says Neeraj Agarwal, MD.
Findings from recent studies support the use of artificial intelligence-based tools in the context of radiation therapy for patients with localized prostate cancer, according to Neeraj Agarwal, MD.
Germline testing may elucidate important mutations in patients with metastatic prostate cancer who may be eligible to receive treatment with PARP inhibitors, according to Neeraj Agarwal, MD.
Related Content