Dr Saad on the Efficacy and Safety of Darolutamide Plus ADT in mHSPC

Fred Saad, CQ, MD, FRCS, FCAHS, director, Prostate Cancer Research, Montreal Cancer Institute; full professor, Department of Surgery, Université de Montréal; uro-oncologist, Urology Department, CHUM, discusses efficacy findings from the global phase 3 ARANOTE trial (NCT04736199) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Notably, this trial evaluated the combination of darolutamide (Nubeqa) plus androgen-deprivation therapy (ADT) vs ADT alone, and findings were presented at the 2024 ESMO Congress.

Eligible patients with mHSPC were randomly assigned in a 2:1 ratio to receive either darolutamide at 600 mg twice daily (n = 446) or placebo (n = 223), both in combination with ADT. The primary end point of the study was radiological progression-free survival. Secondary end points included overall survival (OS), time to the start of subsequent anticancer therapy, time to castration-resistant prostate cancer (CRPC), time to prostate-specific antigen (PSA) progression, time to pain progression, and safety outcomes.

Saad begins by stating that investigators were pleased with the results of the study, as the trial successfully met its primary end point. The combination of darolutamide and ADT reduced the risk of radiographic progression or death by 46% compared with placebo plus ADT, translating to a hazard ratio of 0.54 (95% CI, 0.41-0.71; P < .0001). This clearly demonstrates a delay in disease progression or death, he says. Moreover, all subgroups within the study—including patients with de novo disease and those with high-volume disease, both comprising over 70% of the population—experienced benefits from the addition of darolutamide to ADT compared with ADT alone. Additionally, all secondary end points favored the combination therapy, Saad explains.

Although OS data are still immature, investigators observed a 19% reduction in the risk of death with the darolutamide regimen vs ADT alone, he continues. Other key end points also supported the efficacy of the addition of darolutamide to ADT, including delaying the onset of CRPC and slowing pain progression in patients. There was a significant increase in the rate of undetectable PSA levels in the darolutamide arm, with more than a threefold increase in patients reaching the target of less than 0.2 ng/mL, a critical milestone in prostate cancer management, Saad emphasizes. Furthermore, the study showed substantial delays in PSA progression, which plays an essential role in determining future lines of therapy for these patients, he concludes.