Combination of androgen deprivation therapy (ADT) with external beam radiation therapy (EBRT) is a standard of care for patients with intermediate-risk prostate cancer (PCa). However, 6 months of ADT generates multiple side effects impacting quality of life (QoL). Darolutamide (an androgen receptor targeting agent [ARTA]) is associated with low blood-brain barrier penetrance and less drug-drug interaction.
To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa.
The DARIUS trial is a multicenter randomized non comparative phase 2 trial, randomizing the 6-months darolutamide + EBRT arm versus 6-months ADT + EBRT in patients with unfavorable intermediate-risk PCa.
The primary endpoint is a biological response defined as prostate-specific antigen ≤0.1 ng/ml at month six of darolutamide or ADT. The key secondary endpoints are biochemical recurrence-free survival, disease-free survival, safety, and QoL. Ancillary studies using radiomics and genomic classifier are planned. Sixty-two patients will be included.
In this population of patients requiring ADT combined with EBRT, the use of an ARTA alone, such as darolutamide, may demonstrate antitumoral efficacy while minimizing toxicity and maintaining QoL. Limitations are mainly inherent to the open-label design of this study.
Six months of darolutamide + EBRT compared with 6 months of ADT + EBRT may be efficient in terms of a biological response, avoiding toxicity and altered QoL attributable to ADT in patients with unfavorable intermediate-risk PCa.
The ongoing DARIUS clinical trial assesses short-term (6 months) darolutamide treatment in association with external beam radiation therapy in men with localized prostate cancer. The trial investigates whether single-agent darolutamide can improve the biological response while maintaining a favorable tolerability profile.
European urology oncology. 2024 May 15 [Epub ahead of print]
Paul Sargos, Carine Bellera, Rita Bentahila, Marie Guerni, Nicolas Benziane-Ouaritini, Diego Teyssonneau, Nam-Son Vuong, Guillaume Ploussard, Morgan Roupret, Guilhem Roubaud
Department of Radiotherapy, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux Cedex, France. Electronic address: ., Epicene Team, Bordeaux Population Health Research Center, UMR 1219, Inserm, University of Bordeaux, Bordeaux, France; Clinical and Epidemiological Research Unit, Comprehensive Cancer Center, Inserm CIC1401, Institut Bergonié, Bordeaux, France., Department of Radiotherapy, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux Cedex, France., Department of Medical Oncology, Institut Bergonié, Bordeaux, France., Urology Department, Clinique Saint-Augustin, Bordeaux, France., Department of Urology UROSUD, La Croix du Sud Hospital, Toulouse, France., GRC 5 Predictive Onco-Urology Research Group and Urology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France.