Abstract：
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.
摘要：
胆道癌（BTC）患者目前接受一线治疗后预后差，治疗选择有限。在这项研究中,我们试图评估Sintilimab联合安洛替尼作为晚期BTC患者二线治疗方案的可行性和耐受性.符合条件的患者经组织学证实为局部晚期不可切除或转移性BTC，并在招募一线治疗后失败。主要终点是总生存期（OS）。同时,研究了临床结局与基因组谱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例患者连续入选并接受研究治疗。该试验符合其主要终点，中位OS为12.3个月(95%CI：10.1-14.5)。仅有4名(20%)患者观察到3级治疗相关不良事件(TRAEs),没有检测到4级或5级TRAEs。AGO2的突变与明显更长的OS相关。变形杆菌的丰度与较差的临床反应有关。因此,sindilimab联合安洛替尼表现出令人鼓舞的抗肿瘤活性,具有可耐受的安全性,值得在随后针对晚期BTC患者的更大随机试验中进行研究.
