Dr Saad on the FDA Approval of Darolutamide in mCSPC

“The [ARANOTE] study clearly met its primary end point of improving radiographic progression-free survival, [with] a 46% reduction in the risk of progression of metastatic sites. That was very statistically significant, and all the other secondary end points [also] pointed in the right direction.”

Fred Saad, MD, FRCS professor and chair of urology and director of genitourinary oncology at the Centre Hospitalier de l’Université de Montréal, discussed the significance of the FDA approval of darolutamide (Nubeqa) in metastatic castration-sensitive prostate cancer (mCSPC).

On June 3, 2025, the FDA approved darolutamide for the treatment of patients with mCSPC, based on data from the phase 3 ARANOTE trial (NCT04736199), which was a randomized, double-blind, placebo-controlled study that evaluated darolutamide vs placebo in 669 patients with mCSPC receiving concomitant ADT. Notably, in August 2022, the FDA approved darolutamide in combination with docetaxel for the treatment of patients with mCSPC.

ARANOTE met its primary end point, with darolutamide demonstrating a statistically significant improvement in radiographic progression-free survival (rPFS) compared with placebo. Data supporting the approval showed that the median rPFS was not reached (NR; 95% CI, NR–NR) in the darolutamide arm vs 25.0 months (95% CI, 19.0-NR) in the placebo arm HR, 0.54; 95% CI, 0.41-0.71; P < .0001). At 24 months, the rPFS rate was 70.3% with darolutamide vs 52.1% with placebo.

Although the final analysis did not show a statistically significant overall survival (OS) advantage (HR, 0.78; 95% CI, 0.58-1.05), the trend favored darolutamide; the 24-month OS rates were 79.8% for the experimental arm vs 75.5% in the placebo arm. Saad noted that although follow-up duration limited definitive OS conclusions, the observed 20% reduction in the risk of death aligns with expected trends based on earlier data from other trials.

Additional secondary end points also favored the investigational arm, including time to progression to metastatic castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, and reduction in pain progression.

Sadd also explained that darolutamide was well tolerated. The overall safety profile was comparable with the placebo regimen, with no significant increase in adverse effects. Fatigue, a common concern with androgen receptor pathway inhibitors, was not increased and was reported slightly less frequently in the darolutamide arm, he said.