Woods Edward, Le Dat, Jakka Bharath Kumar, Manne Ashish
Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH 432120, USA.
Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J, Solove Institute at The Ohio State University, 460 W 10th Ave, Columbus, OH 43210, USA.
Cancers (Basel). 2022 Apr 25;14(9):2137. doi: 10.3390/cancers14092137.
Biliary tract cancers (BTC) are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line. Newer targets and newer agents for established targets are being investigated, and this may change the BTC management landscape in the coming years from traditional CT to individualized therapy (TT) or ICI-centered combinations. The latter group may occupy major space in BTC management due to the paucity of targetable mutations and a greater toxicity profile.
胆道癌（BTC）通常在晚期被诊断出来，由于全身治疗选择有限，其预后严重。吉西他滨和顺铂联合化疗（GC）十多年来一直是一线标准治疗方案。二线化疗（CT）选择有限。靶向治疗（TT，即成纤维细胞生长因子2抑制剂或FGFR2、异柠檬酸脱氢酶1或IDH-1以及神经营养性酪氨酸受体激酶或NTRK基因融合抑制剂）已取得一定成功，但在所有BTC患者中，只有不到5%的患者适合接受此类治疗。免疫检查点抑制剂（ICI）如帕博利珠单抗的使用在一线仅限于微卫星高度不稳定（MSI-H）患者。TOPAZ-1试验（GC加度伐利尤单抗）的成功前景广阔，目前有多项试验正在进行，可能很快会在一线推出靶向治疗（培米替尼和英菲格拉替尼）以及ICI联合治疗（在微卫星稳定的癌症中与CT或TT联合）。针对已确定靶点的新靶点和新药物正在研究中，这可能会在未来几年改变BTC的治疗格局，从传统的CT治疗转向个体化治疗（TT）或以ICI为中心的联合治疗。由于可靶向突变较少且毒性较大，后一组治疗方案可能在BTC治疗中占据主要地位。
