Impact of darolutamide on local symptoms: Preplanned and post hoc analyses of the ARAMIS trial.

Darolutamide, a structurally distinct androgen receptor inhibitor, significantly reduced the risk of metastasis and death versus placebo in the phase 3 ARAMIS trial (NCT02200614). Using trial data, we assessed the effect of darolutamide on urinary and bowel symptoms.

Nonmetastatic castration-resistant prostate cancer (nmCRPC) patients were randomized 2:1 to darolutamide (n=955) or placebo (n=554). Local symptom control was assessed by first prostate cancer-related invasive procedures and post hoc analyses of time to deterioration in quality of life (QoL) using total urinary and bowel symptoms and individual questions for these symptoms from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module subscales and Functional Assessment of Cancer Therapy-Prostate prostate cancer subscale. Prostate-specific antigen (PSA) responses were correlated with urinary and bowel adverse events.

Fewer patients receiving darolutamide (4.7%) versus placebo (9.6%) underwent invasive procedures, and time to first procedure was prolonged with darolutamide (hazard ratio 0.42; 95% confidence interval 0.28-0.62). Darolutamide significantly (p <0.01) delayed worsening of QoL for total urinary and bowel symptoms versus placebo, mostly attributed by individual symptoms of urinary frequency, associated pain, and interference with daily activities. Adverse events of urinary retention and dysuria were less frequent with darolutamide, and greater PSA response (≥90%, ≥50% and <90%, <50%) among darolutamide-treated patients was associated with lower incidences of urinary retention (2.2%, 4.2%, 5.1%) and dysuria (0.5%, 3.2%, 5.1%), respectively.

Darolutamide demonstrated a positive impact on local disease recurrence and symptom control in patients with nmCRPC, delayed time to deterioration in QoL related to urinary and bowel symptoms, and a favorable safety profile showing similar incidence of urinary- and bowel-related adverse events compared with placebo.

BJU international. 2022 Sep 10 [Epub ahead of print]

Neal D Shore, Arnulf Stenzl, Christopher Pieczonka, Zachary Klaassen, William J Aronson, Lawrence Karsh, Charles J Ryan, Jorge Ortiz, Shankar Srinivasan, Ateesha F Mohamed, Frank Verholen

Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC, USA., Clinic for Urology Tuebingen, Tuebingen, Germany., Associated Medical Professionals, Syracuse, NY, USA., Georgia Cancer Center, Augusta, GA, USA., University of California and VA Medical Center Greater Los Angeles Healthcare System, Los Angeles, CA, USA., The Urology Center of Colorado, Denver, CO, USA., University of Minnesota, Minneapolis, MN, USA., Bayer Healthcare, Whippany, NJ, USA., Bayer Consumer Care AG, Basel, Switzerland.