ASCO GU 2022: A Randomized, Controlled, Phase 3 Study of Darolutamide in Addition to ADT Versus ADT Alone in Metastatic Hormone-Sensitive Prostate Cancer (ARANOTE)

( On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, Trials in Progress Poster Session A focussed on ongoing trials that will contribute to the care of patients with prostate cancer moving forward. Dr. Sharma presented the design of the ARANOTE trial, assessing darolutamide and androgen deprivation therapy (ADT), as compared to ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Numerous randomized, phase 3 trials have shown the efficacy treatment intensification with the addition of docetaxel, abiraterone acetate, enzalutamide, or apalutamide to ADT in improving overall survival and/or radiologic progression-free survival (rPFS) in patients with mHSPC. However, these combinations are associated with an increased risk of adverse events including fatigue, rash, and cardiovascular events.

Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor. To date, darolutamide is indicated for the treatment of patients with non-metastatic castration resistant prostate cancer. In the ARAMIS study informing its use in this population, darolutamide improved both metastasis-free survival and overall survival with a favorable safety profile. Further, compared to other second generation androgen axis inhibitors, darolutamide has a low incidence of central nervous system−related adverse events, which may be explained by its distinct low blood−brain barrier penetration. Additionally, darolutamide has also been shown to have a low potential for drug−drug interactions, allowing flexibility with concomitant medications. In keeping with the study design of LATITUDE, CHAARTED, TITAN, ARCHES, and others, ARANOTE will evaluate the efficacy and safety of darolutamide plus ADT in patients with mHSPC (NCT04736199).

ARANOTE is an international, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. The authors will accrue patients with histologically or cytologically confirmed adenocarcinoma of the prostate who have documented metastatic disease by conventional imaging (eg, computed tomography or magnetic resonance imaging).


Patients must have started ADT ≤12 weeks before randomization. The authors plan to recruit 555 patients who will be randomized in a 2:1 fashion to darolutamide 600 mg twice daily or placebo, plus ADT.


Patients will be stratified by the presence of visceral metastases, assessed by central review, and prior local therapy.

The primary endpoint is radiographic progression free survival (rPFS), as assessed by central review based on RECIST v1.1 for soft tissue metastases and PCWG3 criteria for bone metastases. The authors will further examine secondary endpoints including overall survival, time to castration-resistant prostate cancer, time to initiation of subsequent antineoplastic therapy, time to prostate-specific antigen progression, rates of undetectable PSA, time to pain progression, and safety and adverse events, as assessed using NCI-CTCAE v5.0.

Patients will be evaluated every 12 weeks for efficacy, safety, and quality of life (using the FACT-P questionnaire) during treatment and during active follow-up post treatment. For long-term follow-up, patients will be contacted by telephone every 12 weeks. Recruitment is ongoing, with the first patient first visit was on February 23, 2021. The projected primary completion date is March 2024 with an estimated study completion date of September 2025.

Presented by: Dayanand Sharma, MD, DNB, All India Institute of Medical Sciences, New Delhi, India