Health-related quality of life (HRQoL) outcomes with darolutamide in the phase 3 ARANOTE trial.

5004 Background: Effective and well tolerated treatments to maintain HRQoL are essential for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Darolutamide (DARO) + androgen deprivation therapy (ADT) significantly reduced the risk of radiological progression or death (primary endpoint) by 46% (hazard ratio [HR] 0.54; 95% confidence interval [CI] 0.41–0.71; P <0.0001) vs placebo (PBO) + ADT in ARANOTE (NCT04736199). The incidence of adverse events (AEs) was low and similar to PBO, with fewer study drug discontinuations due to AEs in the DARO vs PBO group (6.1% vs 9.0%). We report HRQoL and pain outcomes in ARANOTE. Methods: Patients were randomized 2:1 to DARO 600 mg twice daily or PBO, with ADT. HRQoL was measured using the Functional Assessment of Cancer Therapy–Prostate (FACT-P). Deterioration in FACT-P total score by ≥10 points was a prespecified exploratory endpoint; deteriorations in FACT-P subscales by ≥3 points were analyzed post hoc . Pain was assessed using the Brief Pain Inventory–Short Form (BPI-SF), including the pain severity and pain interference subscales. Pain progression (secondary endpoint) was defined as an increase of ≥2 points in BPI-SF worst pain score (WPS) from nadir observed at 2 consecutive evaluations ≥4 weeks apart or initiation of opioid use for ≥7 consecutive days. Association of HRQoL and pain progression with prostate-specific antigen (PSA) response was assessed post hoc . HRs and 95% CIs were calculated using a Cox regression model, stratified by visceral disease (present vs absent) and prior local therapy (yes vs no) for FACT-P total score and pain progression, unstratified for FACT-P and BPI-SF subscales and association with PSA. Results: DARO extended time to deterioration in FACT-P total score (overall well-being) by 5.1 months vs PBO: median 16.6 vs 11.5 months; HR 0.76, 95% CI 0.61–0.93. The treatment benefit of DARO in FACT-P total score was strongly driven by longer time to deterioration in the subscales of social/family well-being (HR 0.79, 95% CI 0.64–0.98), functional well-being (0.78, 0.63–0.96), and urinary symptoms (0.78, 0.61–0.99). Additionally, DARO extended time to pain progression vs PBO: HR 0.72, 95% CI 0.54–0.96. In patients treated with DARO, achievement of PSA response <0.2 ng/mL at any time was associated with longer time to deterioration in FACT-P total score and longer time to pain progression vs detectable PSA response (≥0.2 ng/mL) at any time. Conclusions: To our knowledge, DARO is the first and only androgen receptor inhibitor to demonstrate clinically meaningful delays in deterioration of important patient-relevant HRQoL outcomes vs PBO in men with mHSPC. Patients treated with DARO had improvements in overall well-being (FACT-P total score), social/family well-being, functional well-being, urinary symptoms, and pain. Combined with the efficacy and safety profile, these findings suggest that DARO also confers a positive impact on HRQoL. Clinical trial information: NCT04736199 .