In analyses from the phase III ARANOTE trial reported in The Lancet Oncology, Morgans et al found that darolutamide was associated with prolonged times to worsening pain and worsening health-related quality of life (QOL) compared with placebo in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Study Details
In the international double-blind trial, 669 patients with recurrent or de novo mHSPC were randomly assigned 2:1 between February 2021 and June 2022 to receive darolutamide at 600 mg (n = 446) or placebo (n = 223) twice daily, both with investigator’s choice of androgen-deprivation therapy. The primary analysis of the trial showed that darolutamide significantly improved radiologic progression-free survival vs placebo (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.41–0.71). The current analyses assessed time to pain progression (≥ 2-point increase in Brief Pain Inventory–Short Form worst pain score or initiation of opioids for ≥ 7 days) and time to deterioration of overall wellbeing (≥ 10-point decrease in Functional Assessment of Cancer Therapy–Prostate [FACT-P] total score) in the intent-to-treat population.
Key Findings
Median follow-up for the current analyses was 22.8 months in the darolutamide group and 20.3 months in the placebo group.
Compared with the placebo group, the darolutamide group had significantly delayed time to pain progression (HR = 0.72, 95% CI = 0.54–0.96) and significantly delayed time to deterioration in FACT-P total score (HR = 0.76, 95% CI = 0.61–0.94).
The most common grade 3 to 4 adverse events were hypertension (4% of the darolutamide group vs 4% of the placebo group), anemia (3% vs 4%), and increased aspartate aminotransferase (2% vs < 1%). Serious adverse events occurred in 24% vs 24% of patients. One death considered related to treatment was observed in a patient in the darolutamide group (death–not otherwise specified).
The investigators concluded: “Along with the known survival benefits, the clinically meaningful delays in pain progression and time to deterioration of overall wellbeing support consideration of darolutamide plus [androgen-deprivation therapy] as a standard-of-care treatment option in patients with mHSPC.”
Fred Saad, MD, of the Department of Surgery/Urology, Centre Hospitalier de l’Université de Montréal, Montreal, Canada, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Bayer and Orion Pharma. For full disclosures of the study authors, visit thelancet.com.
