Contemporary Tailored Oncology Treatment of Biliary Tract Cancers

Table 1

Completed clinical trials investigating adjuvant therapies following resection of biliary tract cancers.

Trial	Study arms	Phase	Tumour site	Resection margins	Nodal status	Overall survival (months)	Disease recurrence
Positive trials
BILCAP [20]	vs. observation (1 : 1)	III; Open-label	ICC: (19%); PCC: (29%); DCC: (35%); GBC: (18%)	R0: (62%); R1: (38%)	N0: (53%); N1: (47%)	ITT: 51·1 vs. 36·4; HR 0·81 [95% CI 0·63–1·04]; PPA: 53 vs. 36; HR 0·75 [95% CI 0·58–0·97];	Median RFS (months); ITT: 24·4 vs. 17·5; HR 0.75 [95% CI 0·58–0·98]; PPA: 25.9 vs. 17.4; HR 0·70 [95% CI 0·54–0·9];
Negative trials
Takada et al. [16]	Mitomycin C and 5-flurouracil vs. surgery alone	III; Open-label	Pancreas: (34%); Bile duct: (27%); GBC: (28%); Ampulla of Vater: (11%)	Curative: Noncurative:	Not reported	ITT (GBC cohort only): 16.4 vs. 14.1 (); PPA of 5-year survival rate (%) in GBC cohort: 26.0% vs. 14.4%, ()	5-year DFS rate (%) in GBC cohort: 20.3% vs. 11.6%;
PRODIGE 12-ACCORD 18 [19]	vs. observation	III; Open-label	ICC: (44%); PCC: (8%); DCC: (28%); GBC: (20%)	R0: (87%); R1: (13%)	N0: (50%); N1: (36%); N2: (1%); Nx: (13%)	75.8 vs. 50.8; HR 1.08 [95% CI 0.70-1.66];	Median RFS (months): 30.4 vs. 18.5; HR 0.88 [95% CI 0.62-1.25];
BCAT [23]	vs. observation (1 : 1)	III; Open-label	PCC: (45%); DCC: (55%)	R0: (91%); R1: (11%)	N0: (65%); N1: (35%)	62.3 vs. 63.8; HR 1.01 [95% CI 0.70–1.45];	Median RFS (months): 36.0 vs. 36.9; HR 0.93 [95% CI 0.66–1.32];
ESPAC-3 [84]	Fluorouracil/folinic acid vs. gemcitabine vs. observation (1 : 1 : 1)	III; Open-label	Ampullary: (69%); Bile duct: (22%); Other: (8%)	R0: (84%); R1: (16%)	N0: (41%); N1: (59%)	38.9 vs. 45.7 vs. 35.2; HR for FU vs. observation: 0.95 [95% CI 0.71-1.28]; HR for gemcitabine vs. observation: 0.77 [95% CI 0.57-1.05];	Median RFS (months): 23.0 vs. 29.1 vs. 19.5; HR for FU vs. observation: 0.69 [95% CI 0.51-0.95]; HR for gemcitabine vs. observation: 0.68 [95% CI 0.50-0.95];

OS: overall survival; RFS: relapse-free survival; ICC: intrahepatic cholangiocarcinoma; PCC: perihilar cholangiocarcinoma; DCC: distal cholangiocarcinoma; GBC: gallbladder carcinoma; ITT: intention-to-treat; PPA: per protocol analysis; HR: hazard ratio; 95% CI: 95% confidence interval; GEMOX: gemcitabine+oxaliplatin. This subgroup analysis was statistically significant, and therefore, there is a positive finding in the study.