Pathological complete response in advanced intrahepatic cholangiocarcinoma was achieved through tri-modal therapy: A case report and review of literature

Table 1 Studies summarize design and outcomes of HAIC-containing regimens for intrahepatic cholangiocarcinoma treatment

Ref.	Year	Study design	Sample size	Patients	Arms	mOS (m)	ORR (%)	DCR (%)	Conversion rate	TrAEs (Grade 3-4)
Zheng et al[25]	2024	Retrospective	202	ICC	Arm 1: FOLFOX-HAIC +TKI+ PD(L)-1; Arm 2: GC /GEMOX	20.8 vs 14.8	35.5 vs 14.5	77.6 vs 63.2	NA	Elevated AST 145% vs 7.9%; Thrombocytopenia 118% vs 15.8%; Neutropenia 145% vs 14.5%; Abdominal pain 7.9% vs 1.3%
Lin et al[31]	2024	Retrospective	141	ICC	Arm 1: FOLFOX-HAIC+LEN+PD(L)-1; Arm 2: GEMOX/GC +PD(L)-1; Arm 3: GEMOX/GC	NR vs NR vs 21.8	50 vs 18.4 vs 6.0	88.1 vs 73.5 vs 52.0	9.5% (4/42) vs 2.0% (1/49) vs 0.0% (0/50)	Elevated ALT 48% vs 2.0% vs 4.0%; Elevated AST 48% vs 2.0% vs 2.0%; Neutropenia 24% vs 8.2% vs 10.0%; Vomit 0% vs 12.2% vs 14.0%
Li et al[26]	2024	Retrospective	179	ICC	Arm 1: FOLFOX -HAIC + SYS; Arm 2: SYS	15.8 vs 12.7	55 vs 27	84 vs 83	NA	Increased ALT or AST levels; 7.2%; thrombocytopenia 48%
Lin et al[27]	2024	Retrospective	90	ICC	Arm 1: GEMOX; HAIC + LEN + PD-1; Arm 2: GC	16.8 vs 11.0	43.1 vs 20.5	90.2 vs 69.2	NA	Stomach ache 7.8% vs 2.6%; GI bleeding 5.9% vs 2.6%; Hyperbilirubinemia 59% vs 0%; Leukopenia 20% vs 10.3%
Zhao et al[32]	2024	Retrospective	59	ICC	Arm 1: FOLFOX-HAIC + LEN + Durvalumab; Arm 2: GC + Durvalumab	15.8 vs 9.6	76.9.% vs 17.4% (mRECIST)	92.3% vs 56.5% (mRECIST)	NA	Elevated ALT 129% vs 3.6%; Anemia 65% vs 3.6%; Thrombocytopenia 97% vs 7.1%; Abdominal pain 3.2% vs 10.7%
Huang et al[33]	2024	Retrospective	46	ICC	FOLFOX-HAIC + LEN + PD-1	16.77	47.8	91.3	6.5% (3/46)	Neutropenia 217%; Thrombocytopenia 174%; Elevated ALT 130%; Elevated AST 87%
Li et al[34]	2024	Retrospective	34	Hilar CCA	mFOLFOX7-HAIC+ Capecitabine + Camrelizumab	20.0	61.8	97.0	NA	Fatigue 59%; Rash 2.9%
Song et al[35]	2024	Retrospective	28	ICC	mFOLFOX6-HAIC + Toripalimab + Surufatinib	NR	58	79	NA	Abdominal pain 7.2%; Leukopenia 72% Thrombocytopenia 7.2%
Zhao et al[36]	2024	Retrospective	28	ICC	FOLFOX-HAIC + LEN + Durvalumab	17.9	65.2 (mRECIST)	91.31 (mRECIST)	10.7% (3/28)	Elevated ALT 143; Thrombocytopenia 107%; Anemia 71%; Abdominal pain 7.1%
Ni et al[37]	2024	Retrospective	21	ICC	GEMOX-HAIC + GEM + LEN + PD-1	19.5	52.3	76.1	19% (4/21)	Hypertension 28.6%; Hand-foot syndrome 19%; Myelosuppression 14.3%
Yang et al[28]	2023	Retrospective	146	ICC	Arm 1: mFOLFOX-HAIC; Arm 2: GC or GEMOX	18.0 vs 17.8	45.3 vs 21.1 (mRECIST)	88 vs 88.7 (mRECIST)	NA	Abdominal pain 4% vs 0%; Vomit 1.3% vs 11.2%; Neutropenia 13% vs 5.6%; Elevated AST 27% vs 2.8%
Wei et al[38]	2023	Retrospective	55	CCA	Arm 1: FOLFOX-HAIC+LEN+PD-1; Arm 2: FOLFOX-HAIC+LEN	16.0 vs 11.0	28.6 vs 20.0	80 vs 65	HAIC+LEN+PD-1 arm: 17.1% (6/35) vs HAIC+LEN arm: 10% (2/20)	Hypertension 42.9% vs 45%; Immune-mediated pneumonia 86% vs 0%; Hand-foot syndrome 86% vs 20%; GI bleeding 5.7 vs 5%
Wang et al[39]	2023	Retrospective	41	CCA	Arm 1: FOLFOX-HAIC + LEN; Arm 2: FOLFOX-HAIC	32 vs 10	15.8 vs 13.6	84.2 vs 63.6	HAIC + LEN arm 21.0% (4/19) vs HAIC arm 13.6% (3/22)	Hypertension Grade 157% vs 0%; Fever 10.5% vs 0%; Thrombocytopenia 105% vs 4.5%; Leukocytopenia 105% vs 4.5%
Zhang et al[40]	2022	Retrospective	58	ICC	Arm 1: GEMOX-HAIC + TKI + PD-1; Arm 2: TACE + TKI + PD-1	NR	61.5 vs 21.1 (mRECIST)	82.1 vs 36.8 (mRECIST)	15.4% (6/39) vs 0% (0/19)	Elevated AST 154%; Nausea/vomiting 12.8%; Hyperbilirubinemia 128%; Neutropenia 103%
Ishii et al[24]	2022	Retrospective	42	ICC	Arm 1: GEM-FP-HAIC (no prior chemo); Arm 2: GEM-FP-HAIC (post-GC); Arm 3: SC (GC-refractory)	20.6 vs 6.3 vs 3.7	37.5 vs 0 vs NA	75 vs 80 vs NA	NA	Anemia 333%; Thrombocytopenia 222%; leukopenia 56%; Hyperbilirubinemia 56%
Huang et al[30]	2022	Real-World Study	9	ICC	FOLFIRI-HAIC	8	22.2	55.5	NA	Ascites 22.2%; Hyperbilirubinemia 222%; Elevated ALT or AST 222%; Vomit 11.1%
Cai et al[41]	2021	Retrospective	126	ICC	Arm 1: mFOLFOX -HAIC; Arm 2: TACE	19.6 vs 10.8	NA	NA	NA	Myelosuppression 24.6%; Vomit: 10.5%
Kasai et al[42]	2014	Prospective	20	ICC	5-FU-HAIC+ PEG-IFNα-2b	14.6	60.0	90.0	5% (1/20)	Leukopenia 10%; Thrombocytopenia 10%; Anemia 10%

¹DCR was calculated as ORR+SD from paper[36].

LEN: Lenvatinib; GEM: Gemcitabine; SYS: Systemic chemotherapy; GEM-FP: Gemcitabine + Cisplatin + 5-FU; GC: Gemcitabine + Cisplatin; GEMOX: Gemcitabine + Oxaliplatin; TKI: Tyrosine kinase inhibitor; SC: Standard chemotherapy; PEG-IFNα-2b: Pegylated interferon alfa-2b; NR: Not reached; NA: Not available; ICC: Intrahepatic cholangiocarcinoma; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ORR: Objective response rate; DCR: Disease control rate ; TrAE: Treatment-related adverse event.