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2期试验及相关分析

原文发布日期：2025-04-09

英文摘要：

摘要翻译：

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2期试验及相关分析

a phase 2 trial and correlative analysis

原文发布日期：2025-04-09

英文摘要：

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors with limited treatment options. This phase 2 Bayesian study evaluated the combination of regorafenib, a multikinase inhibitor, and avelumab, a programmed death 1 (PD1) ligand 1 inhibitor, in advanced grade 2–grade 3 well-differentiated GEP neuroendocrine tumors or grade 3 GEP neuroendocrine carcinomas after progression on prior therapies. A total of 47 participants were enrolled and 42 were evaluable for efficacy. Participants received regorafenib (160 mg per day) and avelumab (10 mg kg−1 biweekly) in 28-day cycles. The primary endpoint, 6-month objective response rate per the response evaluation criteria in solid tumors version 1.1, was 18% (95% confidence interval (CI): 8–31%), with a median progression-free survival of 5.5 months (95% CI: 3.6–8). Durable responses were noted (16.6 months; 95% CI: 3.7–no response). Treatment-related adverse events were manageable, with fatigue, diarrhea and palmar-plantar erythrodysesthesia being most common. Exploratory biomarker analysis identified PD1 and indoleamine 2,3-dioxygenase 1 expression and activity as potential resistance markers. These findings highlight the clinical potential of regorafenib and avelumab in GEP-NENs, emphasizing the need for predictive biomarkers and validation in future randomized trials. Clinical Trial registration: NCT03475953.

摘要翻译：

GEP-NENs（异质性胃肠道神经内分泌肿瘤）是具有有限治疗选择的局限性分化的肿瘤。这项针对高级别2-3期良性分化神经内分泌肿瘤或3级GEP神经内分泌癌患者进行的阶段2贝叶斯研究，评估了罗格拉芬联合爱伦布林在先前治疗进展后的效果。研究共招募47名受试者，其中42名受试者对疗效可评价。受试者每日服用160 mg罗格拉芬和每周两次10 mg/kg的爱伦布林（每次持续28天）。主要终点为6个月客观缓解率（根据实体瘤反应评估标准V1.1），结果为18%（95%置信区间：8%-31%），中位无进展生存期为5.5个月（95%CI: 3.6-8个月）。耐药性反应被观察到（16.6个月；95%CI: 3.7-无反应）。与治疗相关的不良事件是可以管理的，疲劳、腹泻和手掌-足底血流障碍症是最常见的。探索性的生物标志物分析识别了PD1和吲哚胺2,3-二氧生成酶1表达及活性作为潜在的耐药性标志。这些发现突出了罗格拉芬和爱伦布林在GEP-NENs中的临床潜力，突显了未来随机对照试验中预测生物标志物和验证的必要性。临床试验注册编号：NCT03475953。