Table 5.

Drugs under development for the treatment of intrahepatic, extrahepatic and gallbladder carcinoma of the biliary tract

Gen	Alteration	Prevalence		Method	Level of evidence ESCAT1/ASCO2	Drugs
		EH and gallbladder	IH
IDH1	Mutation	3%	10–20%	NGS		HMPL-306, IDH-305, FT2012 (olutasidenib), AG881 (vorasidenib), LY3410738
IDH2	Mutation	1%	6%	NGS	IIIB1	Enasidenib, LY3410738, AG881 (vorasidenib)
FGFR2	Fusion/rearrangement	1%	4–15%	NGS	IB1	Futibatinib (TAS120), erdafitinib, derazantinib
FGFR2	Other alterations					Futibatinib (TAS120), erdafitinib, derazantinib
NTRK	Fusion/rearrangement	2%	2%	NGS/IHC	IC1 Moderate recommendation 2 Low quality of evidence2	LOXO-195 (selitrectinib) and TPX-00005 (repotrectinib)
MET	Amplification	2–3%	5%	NGS	IIIA1	Tivantinib/crizotinib
PIK3CA	Access point mutation	7%	6%	NGS	IIIA1	MK2206, alpelisib and buparlisib
BRAF	Mutation	3-5%	3%	NGS	IIB1	Dabrafenib and trametinib Belvarafenib
BRCA1/2	Mutations	3%	3–5%	NGS	IIIA1	Olaparib and rucaparib
ERBB2	Amplification/mutation	10–15%	7%	NGS/FISH	IIIA1	Trastuzumab and pertuzumab Zanidatamab Trastuzumab-deruxtecan
TMB	TMB-H	3%	6%-12%	NGS	IIIA1	Pembrolizumab

BRAF B-Raf proto-oncogene, BRCA1/2 breast cancer gene 1 and 2, EH extrahepatic, ERBB2 receptor tyrosine-protein kinase erbB-2, FGFR2 fibroblast growth factor receptor-2, FISH fluorescence in situ hybridization, ICI immune checkpoint inhibitor, IDH1 isocitrate dehydrogenase-1, IDH2 isocitrate dehydrogenase-2, IH intrahepatic, IHC immunohistochemistry, MET mesenchymal epithelial transition factor, NGS next-generation sequencing, NTRK neurotrophic tyrosine receptor kinase, PIK3CA phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha, TMB tumour mutational burden, TMB-H tumour mutational burden-high

¹ESCAT scale for clinical actionability of molecular targets of the European Society for Medical Oncology (ESMO) [28]

² ASCO clinical practice guidelines [45]