Doublet Versus Triplet Therapy in High-volume Metastatic Hormone-sensitive Prostate Cancer Patients with Bone Metastases: Results from the ARON-3 Study

IF 8.5 1区医学 Q1 ONCOLOGY

European urology oncology Pub Date : 2026-08-01 Epub Date: 2026-06-05 DOI:10.1016/j.euo.2026.05.010

Philipp Cornelius Mandel, Mike Wenzel, María Natalia Gandur Quiroga, Maria T. Bourlon, Felix Chun, Zin W. Myint, Laura Bernal, Ray Manneh Kopp, Maria José Juan Fita, Thomas Büttner, Ondrej Fiala, Haoran Li, Martin Bögemann, Tomas Buchler, Diana Matthews, Alessandro Rizzo, Francesco Ciccimarra, Fernando Sabino Marques Monteiro, Andrey Soares, Francesco Massari, Matteo Santoni

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引用次数: 0

Abstract

Background and objective

Data for direct comparison of the outcomes for androgen-deprivation therapy (ADT) + androgen signaling pathway-inhibitors (ARPI) versus ADT + ARPI + docetaxel are scant, especially in patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC), according to CHAARTED classification and regarding to the number of bone metastases.

Design, setting and paticipants

Relying on the multicentric international ARON-3 database, patients with high-volume mHSPC with bone metastases undergoing doublet versus triplet therapy were selected and stratified according to the number of bone metastases (≤10 vs >10). Primary endpoints consisted of time to treatment failure (TTF), prostate-specific antigen-response, and overall survival (OS).

Results and Limitations

Overall, 841 patients treated with doublet (75%) or triplet (25%) therapy were included. At 12 wk, triplet therapy was associated with changes in opioid use and in Eastern Cooperative Oncology Group performance status. Median OS was 63.0 mo for ADT + abiraterone acetate and was not reached for ADT + apalutamide, ADT + enzalutamide, and ADT + docetaxel + darolutamide. Differences in adjusted TTF estimates between treatment groups were observed in patients with >10 bone metastases (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.28–0.87; p = 0.02), whereas adjusted OS estimates also differed numerically but were not statistically significant (HR 0.48, 95% CI 0.21–1.07; p = 0.1). In patients with concomitant visceral metastases, TTF and OS estimates also differed numerically by treatment group; however, these differences were not statistically significant.

Conclusions

In exploratory subgroup analyses, TTF and OS estimates varied by bone metastatic burden, but formal interaction testing did not show evidence of heterogeneity. These findings require prospective validation.

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双联体与三联体治疗骨转移的高容量转移激素敏感前列腺癌患者：来自ARON-3研究的结果

背景和目的：根据CHAARTED分类和骨转移数量，雄激素剥夺治疗(ADT) +雄激素信号通路抑制剂（ARPI）与ADT + ARPI +多西他赛直接比较结果的数据很少，特别是在高容量转移性激素敏感前列腺癌（mHSPC）患者中。设计、环境和参与者：依托多中心国际ARON-3数据库，选择高容量mHSPC骨转移患者，并根据骨转移数量（≤10 vs bbb10）进行双重或三重治疗和分层。主要终点包括治疗失败时间（TTF）、前列腺特异性抗原反应和总生存期（OS）。结果和局限性：总的来说，841例患者接受双胎（75%）或三胞胎（25%）治疗。在12周时，三联疗法与阿片类药物使用的变化和东部合作肿瘤组的表现状态有关。ADT +醋酸阿比特龙的中位OS为63.0个月，而ADT +阿帕鲁胺、ADT +恩杂鲁胺和ADT +多西他赛+达罗卢胺的中位OS未达到。在bbb10骨转移患者中，治疗组间校正后的TTF估计值存在差异（风险比[HR] 0.49, 95%可信区间[CI] 0.28-0.87; p = 0.02），校正后的OS估计值也存在数值差异，但无统计学意义（HR 0.48, 95% CI 0.21-1.07; p = 0.1）。在伴有内脏转移的患者中，TTF和OS估计值在治疗组之间也存在数值差异；然而，这些差异没有统计学意义。结论：在探索性亚组分析中，TTF和OS估计因骨转移负荷而异，但正式的相互作用测试没有显示异质性的证据。这些发现需要前瞻性验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European urology oncology Multiple-

CiteScore

15.50

自引率

2.40%

发文量

128

审稿时长

20 days

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