KEY TAKEAWAYS
- The phase 3 ARAMIS rollover study analyzed the long-term safety and tolerability of DARO in pts with nmCRPC.
- 954 pts with nmCRPC were administered DB DARO 600 mg (orally, twice daily).
- The study confirms that DARO effectively enhances metastasis-free survival by almost two years and lowers the risk of death by 31% in nmCRPC patients compared to placebo.
The ARAMIS study administered double-blind (DB) darolutamide (DARO) 600 mg (orally, twice daily) to 954 patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). Of the enrolled pts, 591 continued on open-label (OL) DARO after the primary analysis. After completing the ARAMIS study, 294 pts displayed no evidence of metastases and entered the ROS. The treatment duration and safety of DARO were reported for all 954 pts across the DB, DB+OL, and DB+OL+ROS periods.
Based on the data cut-off of January 31, 2022, it was found that DARO treatment length varied by regimen. DB: 1.5 years (0-4), DB+OL: 2.1 years (0-4.9), DB+OL+ROS: 2.8 years (0-6.8). 32.3% (954 pts) administered DARO therapy for ≥2–<4 years, 17.3% for ≥4–<5 years, and 12.8% for ≥5 years. It was documented that treatment-emergent adverse events (TEAEs) increased over time. The statistics of TEAEs for DB, DB+OL, and DB+OL+ROS periods demonstrate this trend: any grade 85.7%, 89.8%, 91.5%; grade 3/4 26.3%, 31.8%, 35.5%; serious 26.1%, 32.1%, 38.5%; and leading to treatment discontinuation 8.9%, 10.5%, 12.9%. The study showed minimal TEAEs incidences usually associated with androgen receptor inhibition across the DB, DB+OL, and DB+OL+ROS periods. During the initial 24 months of DARO therapy, incidences of most of these TEAEs were low and ≤2% different vs placebo, barring fatigue. The onset of these TEAEs by time intervals across all study phases (DB, DB+OL, DB+OL+ROS) were presented.
Notably, over 30% of pts diagnosed with nmCRPC received DARO treatment for ≥4 years, demonstrating long-lasting clinical benefits. Most adverse events were seen within the first two years of treatment, and the frequency of such events remained relatively low over time. DARO has a consistently positive safety profile, even with prolonged exposure. ROS did not detect any new safety concerns.
Source: https://www.auajournals.org/doi/10.1097/JU.0000000000003226.14
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04464226
Shore, Neal D.; Luz, Murilo; Ulys, Albertas; Ortiz, Jorge; Srinivasan, Shankar; Kurland, Etah; Fizazi, Karim MP11-14 TREATMENT DURATION AND LONG-TERM SAFETY AND TOLERABILITY WITH DAROLUTAMIDE IN NONMETASTATIC CASTRATION-RESISTANT PROSTATE CANCER (nmCRPC): ARAMIS ROLLOVER STUDY, Journal of Urology: April 2023 – Volume 209 – Issue Supplement 4 | doi: 10.1097/JU.0000000000003226.14.
