Fred Saad, MD, on darolutamide outcomes across comorbidity burdens

At the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium, Fred Saad, MD, FRCS, discussed findings from a post hoc analysis of the phase 3 ARANOTE trial (NCT04736199) evaluating the impact of comorbidities and concomitant medications on outcomes with darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC).¹ Saad is a professor and chief of urology at University of Montreal Hospital Center.

In the ARANOTE trial, patients with mHSPC were randomly assigned to darolutamide plus ADT vs placebo plus ADT. The study demonstrated a significant improvement in radiographic progression-free survival (rPFS) with the addition of darolutamide, along with benefits in secondary end points such as delayed progression to castration-resistant disease, improved PSA responses, delayed pain progression, and prolonged quality of life. In the post hoc analysis presented at the meeting, investigators specifically examined whether these benefits were influenced by comorbidities and concomitant medications at baseline.

Results showed that the efficacy of darolutamide was consistent regardless of the number or type of baseline comorbidities or concomitant medications. Across subgroups defined by fewer or greater comorbid conditions (≤4, HR, 0.46; 95% CI, 0.32 to 0.65; >4, HR, 0.58; 95% CI, 0.36 to 0.93) or medications (≤4, HR, 0.48; 95% CI, 0.32 to 0.72; >4, HR, 0.61; 95% CI, 0.38 to 0.97), darolutamide maintained an rPFS benefit compared with ADT alone, with hazard ratios consistently favoring treatment. Importantly, this benefit extended to patients with common age-related conditions, including cardiovascular, musculoskeletal, and metabolic disorders (HR range: 0.35 to 0.62). Safety findings were similarly reassuring, with comparable rates of treatment-emergent adverse events across subgroups.

According to Saad, these findings have important implications for clinical practice, particularly for urologists who often serve as the initial point of care for patients with advanced prostate cancer. Despite historical reliance on ADT alone, the data reinforce that treatment intensification with an androgen receptor pathway inhibitor should be considered standard of care in mHSPC. He emphasized that concerns about comorbidities or drug interactions should not preclude intensification, and encouraged collaboration with medical oncologists when needed to ensure patients receive optimal, evidence-based therapy.

REFERENCE

1. Saad F, Haresh KP, Vjaters E, et al. Efficacy and safety of darolutamide and ADT in patient subgroups by baseline comorbidities and concomitant medications: ARANOTE post hoc analyses. J Clin Oncol. 2026. 44;(suppl 7; abstr 178)