Rapid Readouts: Extended Follow-up From the Phase 3 ARAMIS trial

Neal Shore, MD, discusses data from the following presentation:

• DARO tolerability and treatment response in the extended follow-up of the phase 3 ARAMIS trial (Shore, ASCO 2021, abstract 5079)
  • The study’s objective is to examine the tolerability and treatment response data of DARO treatment in men with high-risk, nonmetastatic, castration-resistant prostate cancer from the extended follow-up of the phase 3 ARAMIS trial (NCT02200614).
  • Phase 3 trial extended follow-up:
    • Comparator arm: DARO (600 mg) 2x daily
    • Control arm: placebo (2 matching tablets) 2x daily

• After primary analysis for metastasis-free survival, patients could continue onto an open-label trial with DARO treatment

• Extended follow-up end points examined dose tolerability and treatment response by pharmacodynamic modeling and landmark sensitivity analysis

• Conclusions: Treatment response
• DARO is a structurally distinct androgen receptor inhibitor that demonstrated benefits in:
  • Prostate-specific antigen (PSA) response. Occurred in 84.0% and 84.5% of patients treated with DARO in the double-blind and double-blind-plus-open-label treatment periods, respectively, vs 7.9% of patients treated with placebo
    • A PSA response was noted in 31.6% of patients who crossed over from placebo to DARO treatment in the open-label treatment period.
  • Survival. 95% of patients treated with DARO in the initial treatment period were alive after 2 years.
    • Pharmacodynamic modeling demonstrated a positive association between a longer overall survival (OS) and maximum PSA decline in patients treated with DARO.
    • A landmark sensitivity analysis at week 16 demonstrated a further positive association between maximum PSA decline at week 16 and subsequent OS.
• Conclusions: Safety and tolerability
• DARO treatment was well tolerated in both the double-blind and open-label treatment periods within the ARAMIS study.
  • Similar rates of discontinuation were noted in both treatment periods due to adverse events in the DARO and the placebo-treated groups (8.9% and 8.7%, respectively).
  • A lower rate of discontinuation due to disease progression was noted in the DARO arm vs the placebo-treated group (12.5% vs 25.3%, respectively) during the double-blind treatment period; similar discontinuation rates were noted in the extended follow-up for both the double-blind and open-label treatment periods (12.6% each)
  • 98.8% of patients in the trial received the full planned dose of DARO (in both the double-blind and open-label periods), with all patients who required dose adjustments able to reescalate to the full treatment dose.
  • No significant cardiovascular or neurological safety events were noted in the extended follow-up, however a slight increase in fatigue was reported.
• In the ARAMIS trial, treatment with DARO demonstrated a favorable tolerability and safety profile, which will have clinical use implications.