Dr Saad on the Efficacy of Darolutamide Plus ADT In Low and High Volume mHSPC

“When we look at the primary end point of the study, we see that there was a 40% reduction in the risk of radiographic progression in [those with] high volume disease and a 70% reduction risk of radiographic progression in the low volume [group]. [This shows that] both groups benefited, but it looks like earlier [treatment] is better if we can treat patients with low volume disease.”

Fred Saad, CQ, MD, FRCS, FCAHS, director, Prostate Cancer Research, Montreal Cancer Institute, Centre Hospitalier de l’Université de Montréal; full professor, Department of Surgery, Université de Montréal; and uro-oncologist, Urology Department, University of Montreal Health Center, discusses efficacy and safety of darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) according to disease volume in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase 3 ARANOTE trial (NCT04736199).

Results from this subgroup analysis were presented at the 2025 Genitourinary Cancers Symposium and demonstrated benefit with darolutamide in combination with ADT without docetaxel regardless of whether patients had low or high disease volume. In the study, 71% of patients had high-volume disease (n = 472) and 29% had low-volume disease (n = 197).

The combination reduced the risk of radiographic progression by 40% in the high-volume group and by 70% reduction in the low-volume group, Saad reports. This substantial benefit with darolutamide plus ADT was generally consistent across subgroups, with a potentially greater advantage when treating patients with low-volume disease earlier in the disease course, he notes.

Secondary end points, including time to metastatic castration-resistant prostate cancer (mCRPC) and time to prostate-specific antigen (PSA) progression, were significantly delayed with the darolutamide combination vs placebo regimen in both subgroups, with a more pronounced benefit in patients with low-volume disease, Saad continues. PSA response rates were also improved with the addition of darolutamide, he adds. In the high-volume group, 55% and 83% of patients in the low- and high-volume subgroups, respectively, achieved undetectable PSA levels at any time point with the combination. This is substantially higher than what is typically observed with ADT alone, Saad states.

Overall, this analysis adds to the growing evidence supporting the use of androgen receptor pathway inhibitors in the treatment of patients with mHSPC and expands the arsenal of these agents for this patient population, he concludes.