Advances in the management of cholangiocarcinoma

Table 1 Targetable genomic alterations in cholagiocarcinoma under investigation

Alterations	iCCA	pCCA/dCCA	Products under investigation
FGFR fusion	15%-20%	< 5%	Pemigatinib1, Derantinib (ARQ-087), Infigrantinib1 (BGJ398), Erdafitinib, TAS-120, ADZ4547
IDH1/2 mutation	20%	< 5%	Ivosidenib1, Enasidenib (AG-221), BAY 1436032, IDH305
ErbB2 (HER-2) amplification	< 5%	10%-15%	Trastuzumab, iapatinib, TAS0728, A166, PRS-343, ZW25
BRAF mutation	5%	< 5%	Dabrafenib + trametinib
DNA damage repair gene mutation (ARID1A, BRCA1/2)	25%	10%-15%	PARP inhibitors (olaparib, rucaparib)

¹FDA approved.

iCCA: Intrahepatic cholangiocarcinoma; pCCA: Perihilar cholangiocarcinoma; dCCA: Distal cholangiocarcinoma; FGRR: Fibrobast growth factor receptor; IDH: Isocitrate dehydrogenase; ERBB (HER-2): A subtype of epidermal growth factor receptor tyrosine kinase; BRAF: Gene for serine/threonine-protein kinase B-Raf; ARID1A: Gene encoding a swItch/sucrose non-fermentable ATP-dependent chromatin remodeling complex; BRCA: Breast cancer gene.

Table 2 Role of treatment modalities in the management of cholangiocarcinoma

Tumor location	Surgery	Liver transplantation	Systemic therapy			Radiation therapy
			NeoAdjuvant	Adjuvant	Palliative
Intrahepatic	Liver resection is first line management, anatomic resection is preferred	Clinical trials and select centers only	Not indicated	Capecitabine	Gemcitabine/Cisplatin; FOLFOX or evaluate for targetable mutations	External beam radiation reduces recurrence in R1 resection
Perihilar	Liver resection is first line management	Consider if not resection candidate, PSC	Only prior to liver transplant	Capecitabine	Gemcitabine/Cisplatin; FOLFOX	External beam radiation required pre liver transplant
Distal	Pancreaticoduodenectomy is first line management	Not indicated	Not indicated	Capecitabine	Gemcitabine/Cisplatin; FOLFOX	No defined role

PSC: Primary sclerosing cholangitis; FOLFOX: Leucovorin, fluorouracil, and oxaliplatin.