Biliary tract cancer (BTC) compromises a heterogenous group of tumors with poor prognoses. Curative surgery remains the first choice for localized disease; however, most BTC patients have had unresectable or metastatic disease. The gold standard therapy for these patients is chemotherapy with gemcitabine and cisplatin. There are no consensus guidelines for standard treatment in a second-line setting, although the data of the ABC-06 trial showed a slight survival benefit from oxaliplatin and 5-fluorouracil combination chemotherapy. Recent progress in comprehensive genomic profiling for advanced BTC (ABTC) has helped to clarify tumorigenesis and facilitate the coming era of precision medicine. Generally, targeted agents fail to show significant clinical benefits in unselected populations. Only fibroblast growth factor receptor 2 (FGFR2) fusion and isocitrate dehydrogenase (IDH)- and BRAF mutation-enriched populations have survival benefits from the corresponding inhibitors. Several interesting targeted agents for monotherapies or combination therapies with other compounds are currently ongoing or recruiting. Here, we review the published data from clinical trials of second-line therapies after the failure of gemcitabine-based chemotherapy in ABTC. The results were stratified by different genetic alternations, as well as by chemotherapy, targeted therapy and immunotherapy.

中文翻译：

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开发针对吉西他滨耐药性胆道癌的可能的下一代系统疗法：临床试验的视角

胆道癌（BTC）是一组预后不良的异质性肿瘤。根治性手术仍然是局部疾病的首选；然而，大多数 BTC 患者患有无法切除或转移的疾病。这些患者的金标准治疗是吉西他滨和顺铂化疗。尽管 ABC-06 试验的数据显示奥沙利铂和 5-氟尿嘧啶联合化疗可带来轻微的生存获益，但二线标准治疗尚无共识指南。先进 BTC (ABTC) 综合基因组分析的最新进展有助于阐明肿瘤发生并促进精准医疗时代的到来。一般来说，靶向药物在未选择的人群中无法显示出显着的临床益处。只有成纤维细胞生长因子受体 2 ( FGFR2 ) 融合以及异柠檬酸脱氢酶 ( IDH ) 和BRAF突变丰富的群体才能从相应的抑制剂中获得生存获益。目前正在开发或招募几种用于单一疗法或与其他化合物联合疗法的有趣靶向药物。在这里，我们回顾了 ABTC 中基于吉西他滨的化疗失败后二线疗法临床试验的已发表数据。结果根据不同的基因变异以及化疗、靶向治疗和免疫治疗进行分层。