Intrahepatic cholangiocarcinoma (CC) accounts for approximately 20% of all biliary tract cancer (BTC) cases and 10–15% of all primary liver cancer cases. Many patients are diagnosed with unresectable BTC, and, even among patients with resectable BTC, the 5-year survival rate is approximately 20%. The BTC incidence rate is high in Southeast and East Asia and has increased worldwide in recent years. Since 2010, cytotoxic chemotherapy, particularly combination gemcitabine + cisplatin (ABC-02 trial), has been the first-line therapy for patients with BTC. In 2022, a multicenter, double-blind, randomized phase 3 trial (TOPAZ-1 trial) examined the addition of programmed death-ligand 1 immunotherapy (durvalumab) to combination gemcitabine + cisplatin for BTC treatment, resulting in significantly improved survival without notable additional toxicity. As a result of this trial, this three-drug combination has become the new standard first-line therapy, leading to notable advances in BTC management for the first time since 2010. The molecular profiling of BTC has continued to drive the development of new targeted therapies for use when first-line therapies fail. Typically, second-line therapy decisions are based on identified genomic alterations in tumor tissue. Mutations in fibroblast growth factor receptor 1/2/3, isocitrate dehydrogenase 1/2, and neurotrophic tyrosine receptor kinase A/B/C are relatively frequent in intrahepatic CC, and precision medicines are available that can target associated pathways. In this review, we suggest strategies for systemic pharmacotherapy with a focus on intrahepatic CC, in addition to presenting the results and safety outcomes of clinical trials evaluating immune checkpoint inhibitor therapies in BTC.
肝内胆管癌（CC）约占所有胆道癌（BTC）病例的20%，占所有原发性肝癌病例的10%-15%。许多患者被诊断为不可切除的BTC，即使在接受了可切除BTC手术治疗的患者中，5年生存率也仅为约20%。东南亚和东亚地区的BTC发病率较高，近年来全球范围内该病发病率也在上升。自2010年以来，细胞毒性化疗（尤其是吉西他滨联合顺铂，即ABC-02试验）一直是BTC患者的一线治疗方案。2022年，一项多中心、双盲、随机III期临床试验（TOPAZ-1试验）评估了在吉西他滨联合顺铂治疗基础上增加程序性死亡配体1免疫疗法（度伐利尤单抗）用于BTC治疗的效果，结果显示其显著提高了生存率且未见明显的附加毒性。基于这一试验结果，三药联合方案成为自2010年以来BTC治疗的全新标准一线疗法，实现了治疗领域的重大进展。BTC的分子图谱分析持续推动着新靶向治疗药物的研发，以用于一线治疗失败后的治疗选择。通常，二线治疗决策基于肿瘤组织中检测到的基因组改变。肝内胆管癌中成纤维细胞生长因子受体1/2/3、异柠檬酸脱氢酶1/2及神经营养酪氨酸受体激酶A/B/C的突变相对常见，目前已有针对相关通路的精准药物。本综述将重点针对肝内胆管癌提出系统性药物治疗策略，同时总结评估BTC免疫检查点抑制剂治疗的临床试验结果及安全性结局。
New Era of Immune-Based Therapy in Intrahepatic Cholangiocarcinoma
肿瘤(癌症)患者之家