Combining of chemotherapy with targeted therapy for advanced biliary tract cancer: A systematic review and meta-analysis

Table 1 Characteristics of trials included in the analysis

Ref.	NCT number	Country/regions	Study period	Number of patients		Chemotherapy regimen
				CT	CT + TT
Valle et al[1], 2021	NCT02711553	18 countries and regionsa	May, 2016 to Aug, 2017	101	106	CisGem
					102
Vogel et al[17], 2018	NCT01320254	Germany	Jul, 2011 to Dec, 2015	28	62	CisGem
Leone et al[18], 2016	NCT01389414	Italy	Jun, 2010 to Sept, 2013	44	45	GemOx
Valle et al[19], 2015	NCT00939848	UK	Apr, 2011 to Sept, 2012	60	62	CisGem
Santoro et al[21], 2015	NCT00753675	Italy	Oct, 2008 to Sept, 2012	56	58	Gemcitabine
Chen et al[20], 2015	NCT01267344	China	Dec, 2010 to May, 2012	60	62	GemOx
Moehler et al[22], 2014	NCT00661830	Germany	May, 2008 to Jul, 2011	48	49	Gemcitabine
Malka et al[23], 2014	NCT00552149	France and Germany	Oct, 2007 to Dec, 2009	74	76	GemOx
Lee et al[24], 2012	NCT01149122	South Korea	Feb, 2009 to Aug, 2010	133	135	GemOx

^a18 countries and regions include United States, Taiwan, South Korea, Turkey, Argentina, France, Russia, Spain, United Kingdom, Germany, Australia, Belgium, Hungary, Czech Republic, Sweden, Mexico, Denmark, Austria.

CT: Chemotherapy; TT: Targeted therapy; CisGem: Gemcitabine combined with Cisplatin; GemOx: Gemcitabine combined with Oxaliplatin; ORR: Overall response rate; OS: Overall survival; PFS: Progression-free survival.

Table 2 Patient characteristics in the included studies

Ref.	Design	Age, median	Males/females	ECOG 0/1-2	Locally advanced/metastatic	Primary tumour site
Valle et al[1], 2021	CisGem	59	53/48	61/39	2/98	iCCA, 55; GBC, 26; eCCA, 14; AoV, 5
	Ramucirumab	64	46/60	45/58	3/103	iCCA, 56; GBC, 24; eCCA, 18; AoV, 8
	Merestinib	62	48/54	52/50	4/98	iCCA, 60; GBC, 22; eCCA, 14; AoV, 6
Vogel et al[17], 2018	CisGem	59.5	14/14	11/17	5/17	GBC, 3; dCCA, 1; pCCA, 2; iCCA, 20; Others, 6
	Panitumumab	62	36/26	21/39	13/42	GBC, 11; dCCA, 7; pCCA, 2; iCCA, 41; Others, 6
Leone et al[18], 2016	GemOx	64.2	15/29	1/43	6/38	iCCA, 21; eCCA, 7; GBC, 16
	Panitumumab	63.9	17/28	0/45	8/37	iCCA, 21; eCCA, 12; GBC, 12
Valle et al[19], 2015	CisGem	64.5	28/34	28/34	8/54	iCCA, 15; eCCA, 24; GBC, 19; AoV, 4
	Cediranib	68	34/28	27/35	12/50	iCCA, 14; eCCA, 24; GBC, 20; AoV, 4
Santoro et al[21], 2015	Gemcitabine	64	25/31	34/21	NR	iCCA, 29; eCCA, 13; GBC, 7; AoV, 6
	Vandetanib	64.4	31/27	36/23	NR	iCCA, 31; eCCA, 10; GBC, 13; AoV, 4
Chen et al[20], 2015	GemOx	59	30/30	17/43	17/43	iCCA, 45; eCCA, 10; GBC, 5
	Cetuximab	61	28/34	18/44	23/39	iCCA, 44; eCCA, 9; GBC, 9;
Moehler et al[22], 2014	Gemcitabine	64.5	25/23	9/35	NR	GBC, 7; iCCA, 29
	Sorafenib	64	29/20	17/30	NR	GBC, 6; iCCA, 33
Malka et al[23], 2014	GemOx	62	42/32	27/43	15/59	iCCA, 46; eCCA, 14; GBC, 11; AoV, 0
	Cetuximab	61	43/33	35/36	17/59	iCCA, 49; eCCA, 8; GBC, 11; AoV, 1
Lee et al[24], 2012	GemOx	61	79/54	20/113	0/133	CCA, 84; GBC, 47; AoV, 2;
	Erlotinib	59	91/44	26/109	0/135	CCA, 96; GBC, 35; AoV, 4

ECOG: Eastern Co-operative Oncology Group; CisGem: Gemcitabine combined with Cisplatin; GemOx: Gemcitabine combined with Oxaliplatin; iCCA: Intrahepatic cholangiocarcinoma; GBC: Gallbladder carcinoma; eCCA: Extrahepatic cholangiocarcinoma; AoV: Ampulla of Vater; dCCA: Distal cholangiocarcinoma; pCCA: Perihilar cholangiocarcinoma; CCA: Cholangiocarcinoma.