Real-world outcomes of patients with advanced intrahepatic cholangiocarcinoma treated with programmed cell death protein-1-targeted immunotherapy

Figures & data

Table 1. Baseline characteristics.

	N = 42
Age (y), mean ± SD	55.5 ± 10.5
Gender
Male	28 (66.7%)
Female	14 (33.3%)
Aetiology
Hepatitis B	19 (45.2%)
Non-Hepatitis B	23 (54.8%)
Child‐Pugh stage
A	42 (100%)
5	38 (90.5%)
6	4 (9.5%)
ECOG PS
0	5 (11.9%)
1	35 (83.3%)
2	2 (4.8%)
BCLC stage
A	1 (2.4%)
B	4 (9.5%)
C	37 (88.1%)
Extrahepatic metastasis	32 (76.2%)
Lymph node metastasis	18 (42.9%)
Organ metastasis	6 (14.3%)
Lymph node metastasis and organ metastasis	8 (19.0%)
Number of tumour
Single	12 (28.6%)
Multiple	30 (71.4%)
Tumour size (cm)	7.6 ± 3.2
AFP
<400 (ng/ml)	32 (76.2%)
≥400 (ng/ml)	10 (23.8%)
PIVKA-II
≤40 (mAU/mL)	24 (57.1%)
>40 (mAU/mL)	18 (42.9%)
CA19-9
≤35 (U/ml)	19 (45.2%)
>35 (U/ml)	23 (54.8%)
Immunotherapy as systemic
First‐line	35 (83.3%)
Second‐line	7 (16.7%)
Prior treatment
Surgery	7 (16.7%)
TACE	10 (23.8%)
HAIC	22 (52.4%)
Radiation	2 (4.8%)
Chemotherapy	4 (9.5%)
Previous target therapy	7 (16.7%)
Other treatments after PD-1 or combination
Surgery	8 (19.0%)
TACE	10 (23.8%)
HAIC	20 (47.6%)
Ablation	1 (2.4%)
Radiation	4 (9.5%)
Chemotherapy	3 (7.1%)
Sorafenib	1 (2.4%)
Lenvatinib	20 (47.6%)
Apatinib	15 (35.7%)
Regorafenib	1 (2.4%)

ECOG PS: Eastern Cooperative Oncology Group Performance Status; BCLC: Barcelona‐Clinic Liver Cancer; AFP: alpha‐fetoprotein; PIVKA-II: protein induced by vitamin K absence or antagonist-II; CA19-9: Carbohydrate antigen 19-9; TACE: transcatheter arterial chemoembolization; HAIC: hepatic artery infusion chemotherapy.

Table 2. Tumour responses and survival.

	All patients (n = 42)	Nivolumab	Pembrolizumab	Toripalimab	Camrelizumab	Sintilimab	Tislelizumab
Tumour response
CR	4 (9.5%)	0	0	1 (11.1%)	0	3 (21.4%)	0
PR	6 (14.3%)	0	1 (9.1%)	2 (22.2%)	2 (50%)	1 (7.1%)	0
SD	26 (61.9%)	3 (100%)	9 (81.8%)	6 (66.7%)	1 (25%)	7 (50%)	0
PD	6 (14.3%)	0	1 (9.1%)	0	1 (25%)	3 (21.4%)	1 (100%)
ORR (CR + PR)	10 (23.8%)	0	1 (9.1%)	3 (33.3%)	2 (50%)	4 (28.6%)	0
DCR (CR + PR + SD)	36 (85.7%)	3 (100%)	10 (90.9)	9 (100%)	3 (75%)	11 (78.6%)	0
PFS, median (95%CI)	11.6 (95%CI, 7.9–15.3)
TTP, median (95%CI)	11.6 (95%CI, 7.9–15.3)
OS, median (95%CI)	19.3 (95%CI, 14.9–23.7)
6 months survival rate	90.5%
1‐year survival rate	77%
18 months survival rate	57%
2‐year survival rate	19%

CR: complete response; PR: partial response; SD: stable disease; PD: progressive disease; ORR: overall response rate; DCR: disease control rate; PFS: progression‐free survival; TTP: time to progression; OS: overall survival.

Figure 1. Kaplan–Meier curve showing OS and PFS for the whole cohort of patients treated with programmed cell death protein-1 (PD-1)-targeted immunotherapy. (A) OS rates in patients with ICC receiving anti-PD-1 agents. (B) PFS rates in patients with ICC receiving anti-PD-1 agents.

Figure 2. Kaplan–Meier curves showing OS and PFS for patients treated with PD-1-targeted immunotherapy according to radiological tumour response (partial response (PR)/stable disease (SD) vs. progressive disease (PD)). (A) OS rates in patients with or without disease progression. (B) PFS rates in patients with or without disease progression.

Figure 3. Kaplan–Meier curves showing OS and PFS for ICC patients treated with PD-1 monotherapy and PD-1 combination therapy. (A) OS rates in patients with PD-1 monotherapy and PD-1 combined with other treatments. (B) PFS rates in patients with PD-1 monotherapy and PD-1 combination therapy.

Table 3. Adverse events.

Effect	All patients (n = 42)
	Any grade	Grade ≥ 3
Pyrexia	3 (7.1%)	–
Rash	1 (2.4%)	–
Fatigue	1 (2.4%)	–
Anorexia	4 (9.5%)
Palpitation	1 (2.4%)	–
Hiccups	1 (2.4%)	–
Nausea	2 (4.8%)	–
Vomiting	2 (4.8%)	–
Pain	6 (14.3%)	1 (2.4%)
Headache	1 (2.4%)
Low back pain	1 (2.4%)	–
Cough	3 (7.1%)	–
Diarrhoea	2 (4.8%)	–
Abdominal distension	1 (2.4%)
Arthralgia	1 (2.4%)	–
Dental ulcer	2 (4.8%)	–
Hypothyroidism	3 (7.1%)	–
Hypertension	4 (9.5%)
Constipation	2 (4.8%)	–
Hypoproteinemia	1 (2.4%)	–
Myelosuppression	2 (4.8%)	–
Platelet count decrease	2 (4.8%)
Immune associated pneumonia	1 (2.4%)	–
Hand-foot skin reaction	1 (2.4%)	–
Hepatitis	2 (4.8%)	1 (2.4%)
Peripheral neuropathy	1 (2.4%)	–

Figure 4. Kaplan–Meier curves showing OS and PFS for patients with different ALBI grades. (A) OS rates in patients with ALBI grade 1 and grade 2. (B) PFS rates in patients with ALBI grade 1 and grade 2.

Data availability statement

The data that support the findings of this study are available from the corresponding author.