Dr Saad on the Continued Investigation 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 next steps and potential clinical implications for the investigation of darolutamide (Nubeqa) plus androgen-deprivation therapy (ADT) vs ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Findings from the phase 3 ARANOTE trial (NCT04736199), which evaluated the combination, were presented at the 2024 ESMO Congress and demonstrated that combining darolutamide with ADT significantly reduced the risk of radiographic progression or death by 46% compared with placebo plus ADT. This translated to a hazard ratio of 0.54 (95% CI, 0.41-0.71; P < .0001). Moreover, all subgroups, including the 70% of patients with de novo and high-volume disease experienced benefit with the darolutamide and ADT combination. Although overall survival (OS) data are still immature, all secondary end points favored the combination therapy.

The safety and efficacy profile of darolutamide in this trial supports further exploration of the combination in earlier disease settings, such as non-metastatic HSPC, Saad states. He notes that ongoing trials are investigating these potential benefits. Given the safety of darolutamide in combination with other therapies, investigators are optimistic about its use in combination with various agenta without exacerbating adverse effects or drug-drug interactions, Saad adds.

The hope is that darolutamide will soon become a standard of care for MHSPC, complementing the current baseline of ADT plus an androgen receptor pathway inhibitor, Saad continues. With several ARPIs already in use globally, darolutamide would expand therapeutic options, enabling treatment to be tailored to individual patient profiles and preferences, he says. Additionally, its combination with docetaxel offers the flexibility to consider ADT plus darolutamide with or without docetaxel, depending on patient needs, Saad concludes.