Paul Sargos, Carine Bellera, Rita Bentahila, Marie Guerni, Nicolas Benziane-Ouaritini, Diego Teyssonneau, Nam-Son Vuong, Guillaume Ploussard, Morgan Roupret, Guilhem Roubaud
{"title":"短期达罗鲁胺(ODM-201)与放疗同时用于中危前列腺癌患者:Darius(AFU-GETUG P15)2期试验方案。","authors":"Paul Sargos, Carine Bellera, Rita Bentahila, Marie Guerni, Nicolas Benziane-Ouaritini, Diego Teyssonneau, Nam-Son Vuong, Guillaume Ploussard, Morgan Roupret, Guilhem Roubaud","doi":"10.1016/j.euo.2024.04.023","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Outcome measurements and statistical analysis: </strong>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.</p><p><strong>Results and limitations: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Patient summary: </strong>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.</p>","PeriodicalId":12256,"journal":{"name":"European urology oncology","volume":null,"pages":null},"PeriodicalIF":8.3000,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Short-term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients with Unfavorable Intermediate-risk Prostate Cancer: The Darius (AFU-GETUG P15) Phase 2 Trial Protocol.\",\"authors\":\"Paul Sargos, Carine Bellera, Rita Bentahila, Marie Guerni, Nicolas Benziane-Ouaritini, Diego Teyssonneau, Nam-Son Vuong, Guillaume Ploussard, Morgan Roupret, Guilhem Roubaud\",\"doi\":\"10.1016/j.euo.2024.04.023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa.</p><p><strong>Design, setting, and participants: </strong>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.</p><p><strong>Outcome measurements and statistical analysis: </strong>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.</p><p><strong>Results and limitations: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Patient summary: </strong>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. 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Short-term Darolutamide (ODM-201) Concomitant to Radiation Therapy for Patients with Unfavorable Intermediate-risk Prostate Cancer: The Darius (AFU-GETUG P15) Phase 2 Trial Protocol.
Background: 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.
Objective: To assess the efficacy of a combination of 6 months of darolutamide with EBRT to treat patients with unfavorable intermediate-risk PCa.
Design, setting, and participants: 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.
Outcome measurements and statistical analysis: 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.
Results and limitations: 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.
Conclusions: 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.
Patient summary: 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.
期刊介绍:
Journal Name: European Urology Oncology
Affiliation: Official Journal of the European Association of Urology
Focus:
First official publication of the EAU fully devoted to the study of genitourinary malignancies
Aims to deliver high-quality research
Content:
Includes original articles, opinion piece editorials, and invited reviews
Covers clinical, basic, and translational research
Publication Frequency: Six times a year in electronic format