Health Canada approves darolutamide for metastatic castration-sensitive prostate cancer

Health Canada has approved darolutamide (Nubeqa) for use in combination with androgen deprivation therapy (ADT) for the treatment of adult patients with metastatic castration-sensitive prostate cancer (mCSPC), Bayer announced in a news release.¹

With this decision, darolutamide becomes the only androgen receptor inhibitor approved in Canada for mCSPC either with or without docetaxel. The combination of darolutamide plus ADT was also approved in the US in June 2025 as well as in the European Union in July 2025.

"This latest authorization reaffirms Nubeqa's role as a therapy for men with prostate cancer," said Shurjeel Choudhri, senior vice president and head of medical and scientific affairs for Bayer Canada, in the news release.¹ "We extend our thanks to the scientists, doctors, patients, and their families for their contributions that allowed us to offer this new treatment option for metastatic castration-sensitive prostate cancer."

Data on darolutamide plus ADT

The approval is supported by data from the phase 3 ARANOTE trial (NCT04736199), which showed that darolutamide plus ADT significantly extended radiographic progression-free survival (rPFS) compared with placebo plus ADT in patients with mCSPC.²

At 24 months, the rate of rPFS was 70.3% in the darolutamide arm vs 52.1% in the placebo arm, translating to a 46% reduction in the risk of radiographic progression or death (HR, 0.54; 95% CI, 0.41 to 0.71; P < .0001). The median rPFS was not reached (NR) in the darolutamide arm, compared with 25.0 months (95% CI, 19 to NR) in the placebo arm.

According to the authors, all subgroups derived benefit from treatment with darolutamide plus ADT. The HR for high-volume disease was 0.60 (95% CI, 0.44 to 0.80), and the HR for low-volume disease was 0.30 (0.15 to 0.60).

In a final analysis of the data, there was no statistically significant improvement in overall survival (OS) with the addition of darolutamide (HR, 0.78; 95% CI, 0.58 to 1.05). At 24 months, the OS rate was 79.8% in the darolutamide arm and 75.5% in the placebo arm.

In total, the double-blind, global ARANOTE trial included 669 patients who were randomly assigned 2:1 to receive 600 mg darolutamide twice daily plus ADT (n = 446) or to matching placebo plus ADT (n = 223). The median age of participants was 70 years (range, 43 to 93). Among all participants, 31.2% were Asian and 9.7% were Black.

The primary end point for the trial was rPFS. Secondary end points included OS, time to castration-resistant prostate cancer (CRPC), time to prostate-specific antigen (PSA) progression, time to pain progression, time to subsequent systemic anticancer therapy, and safety.

The results from the trial, which were published in the Journal of Clinical Oncology,² also showed improvements in the trial's key secondary end points with the addition of darolutamide.

Specifically, darolutamide was associated with a trend toward clinical benefit in the secondary end points of time to metastatic CRPC (HR, 0.40; 95% CI, 0.32 to 0.51) and time to PSA progression (HR, 0.31; 95% CI, 0.23 to 0.41). Additionally, 62.6% of patients in the darolutamide arm achieved a PSA less than 0.2 ng/mL at any point during the treatment period, compared with 18.5% of patients in the placebo arm.

Time to pain progression (HR, 0.72; 95% CI, 0.54 to 0.96), and time to subsequent systemic anticancer therapy (HR, 0.40; 95% CI, 0.29 to 0.56) were also delayed in the darolutamide arm.

Regarding safety, the combination was well tolerated across both study arms. The incidence of treatment-emergent adverse events (TEAEs) was similar between the 2 groups, with TEAEs leading to permanent discontinuation of the study drug in 6.1% of patients in the darolutamide arm and 9.0% of patients in the placebo/ADT arm. No new safety signals were reported.

"Clinical data from the ARANOTE trial showed that darolutamide is both efficacious and well tolerated as a combination therapy with androgen-deprivation therapy," said principal investigator Fred Saad, MD, FRCS, professor, chairman of surgery, and director of genitourinary oncology at the University of Montreal Hospital Center, in the news release from Bayer.¹ "Today's approval further expands options for how physicians can use Nubeqa in the treatment of mCSPC, giving them greater flexibility in choosing treatment plans for their patients."

REFERENCES

1. Health Canada grants marketing authorization for an additional indication of Bayer’s NUBEQA (darolutamide) for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). News release. Bayer Inc. August 21, 2025. Accessed August 25, 2025. https://www.biospace.com/press-releases/health-canada-grants-marketing-authorization-for-an-additional-indication-of-bayers-nubeqa-darolutamide-for-the-treatment-of-metastatic-castration-sensitive-prostate-cancer-mcspc

2. Saad F, Vjaters E, Shore N, et al; ARANOTE Study Investigators. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. J Clin Oncol. 2024;42(36):4271-4281. doi:10.1200/JCO-24-01798