Darolutamide, an investigational nonsteroidal androgen receptor antagonist, was well tolerated and effective in delaying both pain and worsening of urinary and bowel symptoms in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC), receiving androgen deprivation therapy.
Results from the phase 3 ARAMIS study showed darolutamide, an investigational nonsteroidal androgen receptor antagonist, was well tolerated and effective in delaying both pain and worsening of urinary and bowel symptoms in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC) receiving androgen deprivation therapy. These findings were presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.1,2
The phase 3, randomized, double-blinded ARAMIS study (ClinicalTrials.gov Identifier: NCT02200614) assigned men with high-risk nonmetastatic CRPC already receiving androgen deprivation therapy (2:1) to receive darolutamide (300 mg orally twice daily) or placebo. Previously presented results of the primary study analysis showed significantly longer median metastasis-free survival (the primary end point of the study) in patients in the darolutamide arm compared with patients receiving placebo (40.4 months vs 18.4 months; hazard ratio [HR], 0.41; 95% CI 0.34–0.50; P <.0001).
In addition, a significant improvement in 3-year overall survival (OS) was also observed for the patients receiving darolutamide (83%) vs those who were administered placebo (73%; P =.0452), although this analysis remains immature.1,2
Another important finding of the ARAMIS study was that darolutamide was well tolerated; this determination confirmed prior evidence, which showed low rates of treatment discontinuation and adverse events across study participants.1,2
Also presented were results of other assessments from the ARAMIS trial for secondary and exploratory end points, such as time to prostate-specific antigen (PSA) progression, time to pain progression as measured by the Brief Pain Inventory (Short Form), and time to deterioration of quality of life (QoL) outcomes as assessed by the European Organization for Research and Treatment of Cancer QoL Prostate Cancer module (EORTC-QLQ-PR25), with QoL assessments performed at baseline and every 16 weeks until the end of treatment.1
Of note, the median time to PSA progression was 33.2 months versus 7.3 months in the darolutamide and placebo arms, respectively (P =.0001). Furthermore, time to pain progression was 40.3 months and 25.4 months in patients receiving darolutamide and placebo, respectively (HR, 0.65; 95% CI 0.53–0.79; P < .0001).
Time to deterioration of urinary symptoms, as measured by the EORTC-QLC-PR25, was 25.8 months for patients treated with darolutamide compared with 14.8 months for those receiving placebo (HR, 0.64; 95% CI 0.54–0.76; P <.01), and time to deterioration in bowel symptoms was 18.4 months versus 11.5 months for those receiving darolutamide and placebo, respectively (HR, 0.78; 95% CI, 0.66-0.92; P <.01) using the same measure. However, EORTC-QLC-PR25–related assessments of time to deterioration of hormonal treatment-related symptoms or incontinence showed no significant differences between the 2 groups.1
“We previously established that darolutamide significantly improves metastasis-free survival. Darolutamide [also] has a very favorable safety profile with apparently no side effects associated with other androgen receptor antagonists. We are now showing that darolutamide delays worsening of pain and disease-related symptoms compared with placebo, with maintained Qol. This could make darolutamide an attractive option for men with nonmetastatic CRPC, concluded Dr Fizazi.