Professor Ray McDermott of St. Vincent University Hospital and Tallaght Hospital, Ireland explains the ESMO poster DASL-HiCaP: Darolutamide augments standard therapy for localized very high-risk cancer of the prostate (ANZUP1801). A randomized phase III double-blind, placebo-controlled trial of adding darolutamide to androgen deprivation therapy and definitive or salvage radiation.
Background
Luteinizing hormone-releasing hormone equivalent (LHRHA) radiation therapy (RT) plus androgen deprivation therapy (ADT) is the standard of treatment for men with very high-risk localized prostate cancer (PC) or with very high-risk features and chronic radical prostatectomy (RP) PSA. Despite this, incurable distant metastases in 15 percent of males with very high-risk features evolve within 5 years. Darolutamide is a structurally distinct oral antagonist of the androgen receptor with low penetration of the blood-brain-barrier, low drug-drug interaction potential, and a favorable safety profile. Our aim is to assess the effectiveness of the addition of darolutamide to ADT and RT in the form of either primary definitive therapy or very high-risk PC adjuvant treatment.
Development of the Trial
This study is a randomized (1:1) placebo-controlled, double-blind, phase III trial for men intended for RT with very high-risk localized PC; or very high-risk PSA persistence features or increase within one year after RP. The analysis will be stratified by RP; adjuvant docetaxel use; involvement of pelvic nodals. 1100 participants will be randomized for 96 weeks twice daily with darolutamide 600 mg or placebo. Participants will receive LHRHA from randomization for 96 weeks, plus RT beginning week 8-24. In addition to LHRHA, participants are allowed nonsteroidal antiandrogen (up to 90 days) up until randomization. Early treatment is allowed with up to 6 docetaxel cycles, completed at least 4 weeks before RT. Metastasis-free survival is the primary endpoint, with secondary endpoints of overall survival, PC-specific survival, free survival of PSA development, time to subsequent hormonal therapy, time to castration-resistance, frequency, and severity of adverse events, quality of life associated with health, fear of recurrence. Incremental cost-effectiveness and the detection of prognostic and/or predictive biomarkers of patient response, protection, and resistance to study patients are included in the tertiary endpoints.
Identification of Clinical Trial – ANZUP1801.