Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial.

IF 42.1 1区 医学 Q1 ONCOLOGY Journal of Clinical Oncology Pub Date : 2024-11-10 Epub Date: 2024-08-05 DOI:10.1200/JCO.24.00081
Ethan B Ludmir, Alexander D Sherry, Bryan M Fellman, Suyu Liu, Tharakeswara Bathala, Cara Haymaker, Marina N Medina-Rosales, Alexandre Reuben, Emma B Holliday, Grace L Smith, Sonal S Noticewala, Sarah Nicholas, Tracy R Price, Rachael M Martin-Paulpeter, Luis A Perles, Sunyoung S Lee, Michael S Lee, Brandon G Smaglo, Ryan W Huey, Jason Willis, Dan Zhao, Lorenzo Cohen, Cullen M Taniguchi, Eugene J Koay, Matthew H G Katz, Robert A Wolff, Prajnan Das, Shubham Pant, Albert C Koong, Chad Tang
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Abstract

Purpose: The EXTEND trial tested the hypothesis that adding comprehensive metastasis-directed therapy (MDT) to chemotherapy would improve progression-free survival (PFS) over chemotherapy alone among patients with oligometastatic pancreatic ductal adenocarcinoma (PDAC).

Methods: EXTEND (ClinicalTrials.gov identifier: NCT03599765) is a multicenter, phase II basket trial randomly assigning patients with ≤five metastases 1:1 to MDT plus systemic therapy versus systemic therapy. Disease progression was defined by radiologic criteria (RECIST v1.1), clinical progression, or death. The primary end point was PFS in the per-protocol population, evaluated after all patients achieved at least 6 months of follow-up. Exploratory end points included systemic immune response measures.

Results: Between March 19, 2019, and February 13, 2023, 41 patients were randomly assigned and 40 were eligible for the primary analysis of PFS (19 patients in the MDT arm; 21 patients in the control arm). At a median follow-up time of 17 months, the median PFS time was 10.3 months (95% CI, 4.6 to 14.0) in the MDT arm versus 2.5 months (95% CI, 1.7 to 5.1) in the control arm. PFS was significantly improved by the addition of MDT to systemic therapy (P = .030 for stratified log-rank test) with a hazard ratio of 0.43 (95% CI, 0.20 to 0.94). No grade ≥3 or greater adverse events related to MDT were observed. Systemic immune activation events were associated with MDT and correlated with improved PFS.

Conclusion: This study supports the addition of MDT to systemic therapy for patients with oligometastatic PDAC. Induction of systemic immunity is a possible mechanism of benefit. These results warrant confirmatory trials to refine treatment strategy and provide external validation.

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寡转移性胰腺导管腺癌(EXTEND)在全身治疗的基础上增加转移引导治疗:多中心、随机 II 期试验。
目的:EXTEND试验检验了一种假设,即在化疗基础上增加综合转移导向疗法(MDT)将比单纯化疗改善寡转移性胰腺导管腺癌(PDAC)患者的无进展生存期(PFS):EXTEND(ClinicalTrials.gov标识符:NCT03599765)是一项多中心II期篮子试验,将转移灶≤5个的患者按1:1的比例随机分配给MDT加全身治疗与全身治疗。疾病进展的定义是放射学标准(RECIST v1.1)、临床进展或死亡。主要终点是所有患者随访至少 6 个月后按方案人群的 PFS。探索性终点包括全身免疫反应指标:2019年3月19日至2023年2月13日期间,41名患者被随机分配,40名患者符合PFS主要分析条件(MDT组19名患者;对照组21名患者)。中位随访时间为17个月,MDT治疗组的中位PFS时间为10.3个月(95% CI,4.6-14.0),对照组为2.5个月(95% CI,1.7-5.1)。在全身治疗基础上加用MDT可明显改善PFS(分层对数秩检验P = .030),危险比为0.43(95% CI,0.20至0.94)。未观察到与MDT相关的≥3级或更严重的不良事件。全身免疫激活事件与MDT有关,并与PFS的改善相关:本研究支持对少转移性PDAC患者在全身治疗的基础上加用MDT。诱导全身免疫是一种可能的获益机制。这些结果值得进行确证试验,以完善治疗策略并提供外部验证。
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
Journal of Clinical Oncology
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.
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