Paradigm shift of chemotherapy and systemic treatment for biliary tract cancer

Table 1 Summary of main clinical trials evaluating the targeted therapies in advanced biliary tract cancer patients

Ref.	Country	Drug(s)	Number of patients	Study phase	ORR (%)	Mean OS (months)	Mean PFS (months)	Adverse events
FGFR2 inhibitors
Javle et al[44]	United States, Belgium, Spain, Germany, Singapore, Taiwan, and Thailand	Infigratinib (BGJ398)	108	2	23.1	12.2	7.3	Tiredness, baldness, hyperphosphatemia, and stomatitis
Abou-Alfa et al[45]	United States, France, Italy, Germany, Belgium, and South Korea	Pemigatinib (FIGHT-202)	146	2	35.5	21.1 (FGFR2 fusion)	6.9 (FGFR2 fusion)	Hypophosphatemia, arthralgia, stomatitis, hyponatremia, and abdominal pain
Mazzaferro et al[48]	United States and Italy	Derazantinib (AR087-101)	29	1/2	20.7	12.7	5.7	Fatigue, eye toxicity, hyperphosphatemia, and increase in ALT/AST
Bahleda et al[49]	United States, France, and Spain	Erdafitinib (JNJ-42756493)	11	1	27.0	12.0	7.5	Fatigue, eye toxicity, hyperphosphatemia, and increase in ALT/AST
Goyal et al[51]	United States, France, Spain, United Kingdom, Netherland, Japan, Germany, and South Korea	Futibatinib (TAS-120)	103	2	42.0	21.7	9.0	Hyperphosphatemia, diarrhea, fatigue, alopecia, and stomatitis
IDH inhibitors
Zhu et al[54]	United States, China, Spain, United Kingdom, Ireland, and South Korea	Ivosidenib (AG-120)	187	3	51.0	10.3	2.7	Ascites, anemia, increase bilirubin level, and hyponatremia
BRAF inhibitors
Subbiah et al[59]	United States, Denmark, United Kingdom, Austria, France, Italy, Spain, Germany, Netherland, Switzerland, Japan, and South Korea	Trametinib and Dabrafenib	43	2	47.0	14.0	9.0	Hypertension, reduced white blood cell count, and elevated gamma-glutamyl transferase
NTRK inhibitors
Doebele et al[67]	United States, France, Italy, Spain, Germany, Australia, Hong Kong, Switzerland, Japan, and South Korea	Entrectinib	54	1/2	57.0	21.0	11.0	Anemia, increased weight, dyspnea, and fatigue

BRAF: B-Raf gene; FGFR2: Fibroblast growth factor receptor 2; IDH: Isocitrate dehydrogenase; NTRK: Neurotrophic tyrosine receptor kinase; ORR: Objective response rate; OS: Overall survival; PFS: Progression-free survival; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.