Darolutamide
DASL-HiCaP Study
SUMMARY
The DASL-HiCaP study is an ongoing phase 3, randomized, double-blind, placebo-controlled, multicenter study (N=1106) evaluating the use of darolutamide (n=553) vs placebo (n=553), both in combination with androgen deprivation therapy (ADT) and primary or salvage radiotherapy (RT) in patients with very high-risk localized prostate cancer defined by the study criteria.1,2 Pelvic nodal RT was given to all patients regardless of the pelvic lymph node status.
Baseline characteristics were generally well balanced between patients who received darolutamide and those who received placebo in both the overall population and in the primary and salvage RT cohorts.
At the interim analysis in the darolutamide vs placebo groups, respectively:1
Darolutamide reduced the risk of metastases compared to placebo. The proportion of participants with metastasis-free survival (MFS) (primary endpoint) at 4 years was 95% vs 88% (hazard ratio [HR]: 0.42 [95% confidence interval (CI): 0.27-0.66]; p=0.0001). Of the 27 vs 63 patients who had an MFS event, 33% vs 73% developed metastases, and 67% vs 27% died without prior metastases.
In prespecified subgroup analyses of MFS according to randomization stratification factors and other baseline characteristics, darolutamide showed benefit vs placebo across most subgroups.
- The proportion of participants who were event-free (EF) at 4 years (from baseline) for the secondary efficacy endpoints and post-hoc analyses were: prostate-specific antigen progression-free survival (PSA-PFS), 91% vs 83% (HR: 0.47 [95% CI, 0.33-0.67]); castration-resistant prostate cancer (CRPC), 99% vs 95% (HR: 0.22 [95% CI, 0.09-0.52]); subsequent hormonal therapy, 96% vs 90% (HR: 0.36 [95% CI, 0.21-0.60]); prostate cancer-specific survival (PCSS), 99% vs 99% (HR: 0.58 [95% CI, 0.17-1.97]); overall survival (OS), 97% vs 95% (HR: 0.88 [95% CI, 0.49-1.59]).
- Subsequent therapies were administered to 4% and 10% of patients, primarily ADT (2% vs 8%) and ARPIs (2% vs 7%).
- The incidence of adverse events of special interest (AESIs) was similar in both groups. The most frequent all-grade AEs, reported in >50% of patients in either group, were vasodilation and flushing (66% vs 64%) and fatigue/asthenic conditions (64% vs 57%). Reported AESIs were primarily grade 1-2.
This page is intended for US healthcare professionals and may contain information outside of the approved prescribing information. It is provided in response to an unsolicited request. It is not intended as an endorsement of any usage not contained in the Prescribing Information. This response should be reviewed together with the current full Prescribing Information (including Boxed Warning) and Medical Safety Summary. These materials contain the approved indications, contraindications, warnings and precautions, adverse reactions, and other important safety information for Nubeqa® Darolutamide
Nubeqa is an androgen receptor inhibitor indicated for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), and metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel.
CLINICAL DATA
DASL-HiCaP Study
Study Design/Methods
The DASL-HiCaP study (Darolutamide Augments Standard Therapy for Localised Very HighRisk Cancer of the Prostate; NCT04136353) is an ongoing phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating darolutamide in combination with ADT and primary or salvage radiotherapy (RT) in patients with very high-risk localized prostate cancer defined by the study criteria.1,2 Pelvic nodal RT was given to all patients regardless of the identified pelvic lymph nodes.
Table adapted from slide 5 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
Key: ADT, androgen deprivation therapy; bid, twice daily; LN, lymph node; PSA, prostate-specific antigen; QoL, quality of life; R1:1, randomized 1:1; RP, radical prostatectomy; RT, radiotherapy
Figure was adapted from slide 5 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
Patient Characteristics
- A total of 1106 patients were enrolled between April 2020 and August 2023. Baseline characteristics were generally well balanced between patients who received darolutamide and those who received placebo in both the overall population and in the primary and salvage RT cohorts.
Table was adapted from slides 6-7 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
Efficacy – Interim Analysis
- At the interim analysis, conducted following 87 MFS events, in the overall darolutamide + ADT + RT group and placebo + ADT + RT group, the difference of treatment exposure and RT dose was similar (≤2% difference).1 Patient exposure to study drugs and RT dose delivered are outlined in Table 3: Treatment Exposure.
Table was adapted from slides 8-9 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
- The proportion of patients with metastasis-free survival (primary endpoint) by conventional imaging at interim analysis was significantly (p=0.0001) greater in the darolutamide + ADT + RT group vs placebo + ADT + RT group (Table 4: MFS at Interim Analysis; Figure 2: MFS).
- In prespecified subgroup analyses of MFS according to randomization stratification factors and other baseline characteristics, darolutamide showed benefit vs placebo across most subgroups.
Table was adapted from slide 10 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
Key: ADT, androgen deprivation therapy; CI, confidence interval; HR, hazard ratio; MFS, metastasis-free survival; RT, radiotherapy. Figure adapted from slide 10 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
Key: CI, confidence interval; CTRL, control; DARO, darolutamide; HR, hazard ratio; MFS, metastasis-free survival; PET, positron emission tomography. Figure adapted from slide 11 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
- The proportion of participants who were event-free at the interim analysis for the secondary endpoints and post-hoc analyses are described in Table 5: Secondary Efficacy Endpoints and Post-hoc Analyses at Interim Analysis
Table was adapted from slides 12-17 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
- More patients in the placebo group (10%) received subsequent therapies compared with the darolutamide group (4%) (Table 6: Subsequent Therapies). Administered subsequent therapies from darolutamide group vs placebo group, respectively, were primarily ADT (2% vs 8%) and ARPIs (2% vs 7%).
Table was adapted from slide 16 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
Safety – interim analysis
- The incidence of adverse events of special interest (AESIs) was similar in both groups. The most frequent all-grade AEs, reported in >50% of patients in either group, were vasodilation and flushing and fatigue/asthenic conditions. Reported AESIs were primarily grade 1-2. AESIs are presented in Figure 3: AESIs.
Key: AESI, adverse event of special interest
aOne death each from diagnosis. Total shown are grades 1-5.
Figure adapted from slide 18 in Niazi T, Thomas H, Zhang AY, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Oral presentation presented at: European Society for Medical Oncology (ESMO) Congress; October 23-27, 2026; Madrid, Spain. [downloaded 27 October 2026] Copyrights remain with the original source or as denoted therein.
LITERATURE SEARCH
A literature search of Embase®, PubMed, and/or other resources, including internal/external databases, was conducted pertaining to this topic on 16 October 2026.
REFERENCES
All the references were accessed on the abovementioned literature search date.
- Niazi T, Thomas H, Zhang A, et al. Darolutamide with androgen deprivation therapy (ADT) and definitive or salvage locoregional radiation therapy (RT) for localised, very high-risk prostate cancer: interim analysis of an international, placebo-controlled, randomised phase 3 trial (DASL-HiCaP; ANZUP1801). Poster presented at: European Society of Medical Oncology (ESMO) Congress; October, 23–27, 2026; Madrid, Spain.
- NCT04136353. DASL-HiCaP: Darolutamide Augments Standard Therapy for Localised Very High-Risk Cancer of the Prostate (ANZUP1801): A Randomised Phase 3 Doubleblind, Placebo-controlled Trial of Adding Darolutamide to Androgen Deprivation Therapy and Definitive or Salvage Radiation in Very High Risk, Clinically Localised Prostate Cancer. Updated May 06, 2026, Accessed via https://clinicaltrials.gov/study/NCT04136353
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