Feasibility and tolerability of sintilimab plus anlotinib as the second-line therapy for patients with advanced biliary tract cancers: An open-label, single-arm, phase II clinical trial
Feasibility and tolerability of sintilimab plus anlotinib as the second-line therapy for patients with advanced biliary tract cancers: An open-label, single-arm, phase II clinical trial
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DOI：
10.1002/ijc.34372
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发表时间：
2022-12-01
影响因子：
6.4
通讯作者：
Zong, Hong
中科院分区：
文献类型：
--
作者：
Jin, Shuiling;Zhao, Ruihua;Zong, Hong
目前，胆道癌（BTC）患者一线治疗后预后差，治疗选择有限。在这项研究中，我们试图评估sintiliumab加安洛替尼作为晚期BTC患者二线治疗的可行性和耐受性。合格患者具有组织学证实的局部晚期不可切除或转移性BTC，并且在招募一线治疗后失败。主要终点为总生存期（OS）。同时，探索了临床结果与基因组分析和肠道微生物组之间的关联，以确定该方案的潜在生物标志物。20例患者连续入组并接受研究治疗。试验达到了主要终点，中位OS为12.3个月（95% CI：10.1-14.5）。仅4例（20%）患者观察到3级治疗相关不良事件（TRAE），未检测到4级或5级TRAE。AGO 2突变与OS显著延长相关。变形菌的抑制与较差的临床反应相关。因此，sintilimab加anlotinib表现出令人鼓舞的抗肿瘤活性，具有可耐受的安全性，值得在随后的晚期BTC患者的大型随机试验中进行研究。
Patients with biliary tract cancer (BTC) were associated with poor prognosis and limited therapeutic options after first-line therapy currently. In this study, we sought to evaluate the feasibility and tolerability of sintilimab plus anlotinib as the second-line treatment for patients with advanced BTC. Eligible patients had histologically confirmed locally advanced unresectable or metastatic BTC and failed after the first-line treatment were recruited. The primary endpoint was overall survival (OS). Simultaneously, association between clinical outcomes and genomic profiling and gut microbiome were explored to identify the potential biomarkers for this regimen. Twenty patients were consecutively enrolled and received study therapy. The trail met its primary endpoint with a median OS of 12.3 months (95% CI: 10.1-14.5). Only four (20%) patients were observed of the grade 3 treatment-related adverse events (TRAEs) and no grade 4 or 5 TRAEs were detected. Mutation of AGO2 was correlated with a significantly longer OS. Abundance of Proteobacteria was associated with inferior clinical response. Therefore, sintilimab plus anlotinib demonstrated encouraging anti-tumor activity with a tolerable safety profile and deserved to be investigated in larger randomized trials for patients with advanced BTC subsequently.