Multi-institutional retrospective analysis of FOLFIRI in patients with advanced biliary tract cancers

Table 1 Patient baseline characteristics

Characteristic	Value
Total, n	98
Age in yr, median (range)	60 (22-86)
Gender, n (%)
Female	46 (47)
Male	52 (53)
Institution, n (%)
MD Anderson Cancer Center	61 (62)
University of Michigan	26 (27)
Mayo Clinic Cancer Center	11 (11)
Stage at Treatment with FOLFIRI, n (%)
Locally advanced	24 (25)
Metastatic	74 (75)
Subtype of BTC, n (%)
Extrahepatic cholangiocarcinoma	10 (10)
Intrahepatic cholangiocarcinoma	71 (72)
Gallbladder carcinoma	17 (17)
Line of Therapy, n (%)
First	8 (8)
Second	50 (51)
Third	36 (37)
Fourth or greater	4 (4)
Irinotecan-based regimen, n (%)
FOLFIRI	77 (79)
FOLFIRI + bevacizumab	13 (13)
FOLRIRI + anti-EGFR	5 (5)
FOLFIRINOX	2 (2)
FOLFIRI + nab-paclitaxel	1 (1)
ECOG performance status, n (%)
0	11 (11)
1	48 (49)
2	3 (3)
3	2 (2)
Not documented	34 (35)

BTC: Biliary tract cancer; ECOG: Eastern Cooperative Group; EGFR: Epidermal growth factor receptor; FOLFIRI: Folinic acid, 5-fluorouracil and irinotecan; FOLFIRINOX: Folinic acid, 5-fluorouracil, irinotecan and oxaliplatin.

Table 2 Subgroup analysis of median progression-free survival

Variable	Median PFS (95%CI)	P value	Median OS (95%CI)	P value
Gender
Female	2.4 (1.6–3.6)	0.65	6.6 (4.5–9.9)	0.65
Male	2.3 (1.5–3.4)		6.9 (4.6–10.3)
Subtype of BTC
Extrahepatic cholangiocarcinoma	3.7 (1.5–18.9)	0.14	8.0 (1.8–22.3)	0.61
Intrahepatic cholangiocarcinoma	2.3 (1.9-2.8)		6.5 (4.5–9.7)
Gallbladder carcinoma	2.1 (1.8–3.7)		6.5 (5.2–10.1)
Stage at treatment with FOLFIRI
Locally Advanced	3.2 (2.0–5.2)	0.16	9.3 (5.9–14.7)	0.08
Metastatic	2.1 (1.3–3.3)		5.6 (3.5–8.8)
Line of therapy
First	3.1 (1.4–4.8)	0.24	12.3 (5.6–23.4)	0.08
Second	2.4 (1.8–3.7)		7.7 (4.9–10.5)
Third	2.3 (1.5–3.1)		5.0 (3.6–7.3)
Fourth or greater	1.5 (0.9–2.0)		7.5 (5.2–9.8)
ECOG performance status
0 or 1	2.5 (2.0–3.1)	0.44	7.7 (5.6–11.9)	0.03
2 or greater	1.5 (0.8–4.9)		2.9 (1.7–8.6)
Undocumented	2.1 (1.6–3.4)		5.3 (3.8–8.2)
Genomic analysis
KRAS
Wildtype	2.4 (1.1–5.1)	0.12	11.8 (5.5–25.4)	0.06
Mutant	3.7 (1.7–8.0)		7.5 (3.5–16.1)
FGFR
Wildtype	2.5 (1.0–6.0)	0.29	8.0 (3.3–19.4)	0.56
Fusion	4.3 (1.8–10.5)		13.4 (5.5–32.2)
IDH1
Wildtype	2.7 (1.2–6.0)	0.02	10.8 (4.9–23.9)	0.14
Mutant	2.1 (0.9–4.6)		4.1 (2.3–11.1)

BTC: Biliary tract cancer; ECOG: Eastern Cooperative Group; FOLFIRI: FOLINIC acid, 5-fluorouracil, irinotecan; OS: Overall survival; PFS: Progression-free survival.

Table 3 Genomic profiling by tumor type

Total patients profiled, n = 34	Cholangiocarcinoma		Gallbladder carcinoma, n = 2 (6%)
	Extrahepatic, n = 5 (15%)	Intrahepatic, n = 27 (79%)
Mutation	n (% of profiled)	n (% of profiled)	n (% of profiled)
TP53	-	10 (37)	2 (100)
IDH1	-	8 (30)	-
KRAS	1 (20)	6 (22)	-
FGFR2	2 (40)	4 (15)	-
IDH2	-	2 (7)	-
PBRM1	-	2 (7)	-
BAP1	-	2 (7)	-
NF1	-	1 (4)	1 (50)
ARID1A	-	1 (4)	1 (50)
CDKN2A	-	-	1 (50)
MET	-	1 (4)	-
CCND1	-	1 (4)	-
PBX1	-	1 (4)	-
MYC	-	1 (4)	-
RB1	-	1 (4)	-
MAP3K1	-	1 (4)	-
S76	-	1 (4)	-
SPTA1	-	1 (4)	-
RET	-	1 (4)	-
ALK	-	1 (4)	-
ATM	-	1 (4)	-
CCNE1	-	1 (4)	-
GNAS	-	1 (4)	-
SMAD4	-	1 (4)	-
PIK3CA	-	1 (4)	-
PIK3CB	-	1 (4)	-
PTEN	-	1 (4)	-
PALB2	-	1 (4)	-
ARID2	-	1 (4)	-
BRCA2	-	1 (4)	-
BRAF	-	1 (4)	-
MDM2	1 (20)	-	-
FRS2	1 (20)	-	-