Outcomes of Radium-223 and Stereotactic Ablative Radiotherapy Versus Stereotactic Ablative Radiotherapy for Oligometastatic Prostate Cancers: The RAVENS Phase II Randomized Trial.

IF 42.1 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2025-05-07 DOI:10.1200/JCO-25-00131

Jarey H Wang, Alexander D Sherry, Soha Bazyar, Philip Sutera, Noura Radwan, Ryan M Phillips, Matthew P Deek, Jiayun Lu, Shirl Dipasquale, Curtiland Deville, Theodore L DeWeese, Daniel Y Song, Hao Wang, Robert F Hobbs, Reem Malek, Sara A Dudley, Stephen C Greco, Emmanuel S Antonarakis, Catherine H Marshall, Samuel Denmeade, Channing J Paller, Michael A Carducci, Kenneth J Pienta, Orhan K Oz, Matthew Ramotar, James L Leenstra, Sean S Park, Matthew C Abramowitz, Neil Desai, Alejandro Berlin, Bradley J Stish, Chad Tang, Phuoc T Tran, Ana P Kiess

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引用次数: 0

Abstract

Purpose: Randomized clinical trials (RCTs) have shown progression-free survival (PFS) benefits of metastasis-directed therapy (MDT) without androgen deprivation therapy for oligometastatic castration-sensitive prostate cancer (omCSPC). Most patients with bone metastatic (BM) omCSPC recur with additional bone disease after MDT. We hypothesized the BM-targeting alpha-emitter radium-223 dichloride (Ra223) could target subclinical bone disease and delay progression.

Methods: This is an investigator-initiated, multicenter, open-label phase II RCT. Eligible men with recurrent omCSPC with ≥one bone metastasis (≤three on conventional imaging and/or ≤five on molecular imaging) were randomly assigned (1:1) to stereotactic ablative radiation (SABR) MDT alone or SABR MDT with Ra223 (six cycles). Primary end point was composite PFS.

Results: From August 9, 2019, to March 2, 2023, 64 patients were randomly assigned, 33 to SABR MDT and 31 to SABR MDT/Ra223 balancing for key covariates. Most SABR MDT/Ra223 patients (87%) received six cycles of Ra223. The median PFS was 11.8 months with SABR MDT and 10.5 months with SABR MDT/Ra223 (adjusted hazard ratio [aHR], 1.42 [95% CI, 0.79 to 2.56]; P = .24). Seven patients (11%) experienced grade 3 treatment-related adverse events (no grade 4 or 5), 2 of 33 (6%) with SABR and 5 of 30 (17%) with SABR MDT/Ra223. Patients with high-risk (HiRi) pathogenic mutations in ATM, BRCA1/2, RB1, or TP53 had worse PFS (HR, 5.95 [95% CI, 1.83 to 19.3]; P = .003). Greater T-cell receptor (TCR) unique productive rearrangements were prognostic for improved PFS independent of the treatment arm (aHR, 0.45 [95% CI, 0.21 to 0.96]; P = .04).

Conclusion: Adding Ra223 to SABR MDT in BM omCSPC does not delay progression of disease. We provide evidence for an HiRi mutational signature and TCR repertoire as prognostic biomarkers in omCSPC treated with SABR MDT, highlighting the importance of collecting biological correlates in RCTs for omCSPC.

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镭-223联合立体定向消融放疗与立体定向消融放疗治疗少转移性前列腺癌的疗效：RAVENS II期随机试验

目的：随机临床试验（rct）显示，转移定向治疗（MDT）不采用雄激素剥夺治疗对低转移性去势敏感前列腺癌（omCSPC）的无进展生存（PFS）有利。大多数骨转移性（BM） omCSPC患者在MDT后复发并伴有额外的骨疾病。我们假设靶向脑卒中的α -发射体镭-223二氯化物（Ra223）可以靶向亚临床骨病并延缓进展。方法：这是一项研究者发起的、多中心、开放标签的II期随机对照试验。复发性omCSPC伴有≥1例骨转移（常规影像学≤3例和/或分子影像学≤5例）的符合条件的男性被随机（1:1）分配到单独立体定向消融放疗（SABR） MDT或SABR MDT联合Ra223（6个周期）。主要终点为综合PFS。结果：从2019年8月9日至2023年3月2日，64例患者被随机分配，33例患者接受SABR MDT治疗，31例患者接受SABR MDT/Ra223平衡治疗。大多数SABR MDT/Ra223患者（87%）接受了6个周期的Ra223治疗。SABR MDT组的中位PFS为11.8个月，SABR MDT/Ra223组的中位PFS为10.5个月(校正风险比[aHR]， 1.42 [95% CI, 0.79 ~ 2.56]；P = .24)。7名患者（11%）经历了3级治疗相关不良事件（没有4级或5级），33名患者中有2名（6%）患有SABR， 30名患者中有5名（17%）患有SABR MDT/Ra223。具有ATM、BRCA1/2、RB1或TP53高危（HiRi）致病性突变的患者PFS较差(HR, 5.95 [95% CI, 1.83 ~ 19.3]；P = .003)。较大的t细胞受体（TCR）独特的生产性重排是改善PFS的预后因素，独立于治疗组(aHR, 0.45 [95% CI， 0.21至0.96]；P = .04)。结论：在BM omCSPC的SABR MDT中加入Ra223不会延迟疾病的进展。我们提供了HiRi突变特征和TCR库作为经SABR MDT治疗的omCSPC预后生物标志物的证据，强调了在随机对照试验中收集omCSPC生物学相关性的重要性。

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

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.