Darolutamide Wins Canadian Approval for mCSPC

Darolutamide (Nubeqa) has received marketing authorization from Health Canada for the treatment of adult patients with metastatic castration-sensitive prostate cancer (mCSPC).¹

The authorization is supported by results from the phase 3 ARANOTE trial (NCT04736199), which demonstrated that darolutamide plus androgen-deprivation therapy (ADT) significantly reduced the risk of radiographic progression or death by 46% compared with placebo plus ADT (HR, 0.54; 95% CI, 0.41-0.71; P < .0001). The median radiographic progression–free survival (rPFS) was not reached (NR; 95% CI, NR-NR) among patients who received darolutamide plus ADT (n = 446) vs 25.0 months (95% CI, 19.0-NR) among those who received placebo plus ADT (n = 223).²

The 24-month rPFS rates in these respective arms were 70.3% vs 52.1%. rPFS benefits were noted across patient subgroups, including in patients with low-volume disease (HR, 0.30; 95% CI, 0.15-0.60) and high-volume disease (HR, 0.60; 95% CI, 0.44-0.80).

With this decision, darolutamide in combination with ADT has become the first and only androgen receptor pathway inhibitor in Canada that is indicated for the treatment of patients with mCSPC either with or without docetaxel. Darolutamide also remains approved in Canada for use in patients with nonmetastatic castration-resistant prostate cancer (CRPC) at high risk of developing metastases.

Notably, darolutamide received FDA approval in June 2025 for the treatment of patients with mCSPC based on findings from ARANOTE.³

“Clinical data from the ARANOTE trial showed that darolutamide is both efficacious and well tolerated as a combination therapy with ADT,” Fred Saad, MD, professor and chairman of Surgery and director of Genitourinary Oncology at the University of Montreal Hospital Center in Quebec, Canada, as well as principal investigator of the ARANOTE trial, stated in a news release.¹ “[This] approval further expands options for how physicians can use [darolutamide] in the treatment of mCSPC, giving them greater flexibility in choosing treatment plans for their patients.”

ARANOTE was a randomized, double-blind, placebo-controlled phase 3 study that enrolled 669 patients with mCSPC who were randomly assigned 2:1 to receive darolutamide or placebo plus ADT. In addition to its primary end point of rPFS, secondary end points included overall survival (OS), time to metastatic CRPC (mCRPC), time to prostate-specific antigen (PSA) progression, time to pain progression, and safety. Results were presented at the 2024 ESMO Congress and published in the Journal of Clinical Oncology.

Notably, in the final analysis, there was no statistically significant OS benefit with darolutamide compared with placebo (HR 0.78; 95% CI, 0.58-1.05).² The 24-month OS rate was 79.8% with darolutamide compared with 75.5% with placebo.

However, improvements with darolutamide vs placebo were observed for several other secondary end points, including time to mCRPC (HR, 0.40; 95% CI, 0.32-0.51), time to PSA progression (HR, 0.31; 95% CI, 0.23-0.41), and time to pain progression (HR, 0.72; 95% CI, 0.54-0.96). Moreover, 62.6% of patients who received darolutamide achieved a PSA level lower than 0.2 ng/mL at any time during the treatment period vs 18.5% of those who received placebo.

Regarding safety, the most frequently reported grade 3/4 adverse effects in the darolutamide arm were hypertension (3.6%), anemia (3.6%), pain in extremity (1.8%), bone pain (1.4%), increased alkaline phosphatase levels (1.4%) back pain (0.9%), headache (0.9%), and COVID-19 (0.9%).

“Prostate cancer continues to have a significant effect on men and their families in Canada, with incidence and mortality rates that remain unacceptably high,” Dr Stuart Edmonds, executive vice president for mission, research, and advocacy at the Canadian Cancer Society, concluded in the news release.¹ “Bringing more treatments to patients faster offers new hope, greater choice, and the potential for improved outcomes.”

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 22, 2025. https://www.bayer.com/en/ca/health-canada-grants-marketing-authorization-for-an-additional-indication-of-bayers-nubeqa
2. Saad F, Vjaters E, Shore N, et al. 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
3. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. FDA. June 3, 2025. Accessed June 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer