Efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy in the treatment of advanced biliary malignancies in the first line of chemotherapy

doi:10.12092/j.issn.1009-2501.2026.08.008

Abstract

Abstract:

AIM: To explore the efficacy and safety of programmed cell death protein-1/its ligand-1 (PD-1/PD-L1) inhibitors combined with chemotherapy in the treatment of advanced biliary malignancies in the first line of chemotherapy. METHODS: A retrospective collection of 33 patients with advanced biliary malignant tumors confirmed by histopathology in the First Affiliated Hospital of Anhui Medical University from August 2020 to August 2022 were retrospectively collected, and they were divided into chemotherapy group and chemotherapy combined with PD-1/PD-L1 inhibitor group, and the efficacy was evaluated every 2 treatment cycles, and the safety was evaluated every cycle. The first outcome is PFS and the secondary endpoint is the safety of treatment. RESULTS: Among 16 patients in the chemotherapy group, there were 3 PR cases, 6 SD cases and 7 PD cases, with an ORR rate of 18.8% and a DCR rate of 56.2%. The median PFS was 13.1 weeks. Among 17 patients in the immunotherapy group, there were 8 PR cases, 5 SD cases and 4 PD cases. The ORR rate was 47.1%, the DCR rate was 76.5%, and the median PFS was 21.9 weeks, which was better than the chemotherapy alone. Most of the adverse effects in the two groups were 1-2 grade tolerable, and the difference was not statistically significant. CONCLUSION: PD-1/PD-L1 inhibitors combined with chemotherapy and/or anti-vascular drugs for advanced biliary malignancies have a definite efficacy and is safety, and the treatment with PD-1/PD-L1 inhibitors combined with chemotherapy for advanced biliary malignancies deserves further clinical exploration.

Key words: advanced biliary malignancies, Immune checkpoint inhibitors, chemotherapy, PD-1/PD-L1

CLC Number:

Rong WANG, Yixin ZHOU, Jing XUE, Jiqing HAO, Fan HUANG, Jianghao XING. Efficacy and safety of PD-1/PD-L1 inhibitors combined with chemotherapy in the treatment of advanced biliary malignancies in the first line of chemotherapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(8): 1076-1084.

Figures/Tables 5

References 29

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Item	Chemotherapy (n=16)	Chemotherapy combined with immunotherapy (n=17)	P-value
Gender
Male	7 (43.8%)	12 (70.6%)	0.228
Female	9 (56.3%)	5 (29.4%)
Years
Mean (SD)	59.4 (9.59)	57.8 (7.72)	0.601
Median[Min, Max]	57.5 [42.0, 75.0]	57.0 [45.0, 71.0]
Tumor type
Gallbladder cancer	6 (37.5%)	5 (29.4%)	0.902
Cholangiocarcinoma	10 (62.5%)	12 (70.6%)
Tumor grade
Poorly differentiated	5 (31.3%)	6 (35.3%)	1
Moderately differentiated	11 (68.8%)	11 (64.7%)
MSS
Stable	4 (25.0%)	4 (23.5%)	1
Unclear	12 (75.0%)	13 (76.5%)
Follow-up time (weeks)
Mean(SD)	41.4 (23.9)	35.4 (15.9)	0.41
Median[Min, Max]	39.5 [10.3, 96.6]	30.1 [12.4, 69.4]

Item	Chemotherapy (n=16)	Chemotherapy combined with immunotherapy (n=17)	P-value
Gender
Male	7 (43.8%)	12 (70.6%)	0.228
Female	9 (56.3%)	5 (29.4%)
Years
Mean (SD)	59.4 (9.59)	57.8 (7.72)	0.601
Median[Min, Max]	57.5 [42.0, 75.0]	57.0 [45.0, 71.0]
Tumor type
Gallbladder cancer	6 (37.5%)	5 (29.4%)	0.902
Cholangiocarcinoma	10 (62.5%)	12 (70.6%)
Tumor grade
Poorly differentiated	5 (31.3%)	6 (35.3%)	1
Moderately differentiated	11 (68.8%)	11 (64.7%)
MSS
Stable	4 (25.0%)	4 (23.5%)	1
Unclear	12 (75.0%)	13 (76.5%)
Follow-up time (weeks)
Mean(SD)	41.4 (23.9)	35.4 (15.9)	0.41
Median[Min, Max]	39.5 [10.3, 96.6]	30.1 [12.4, 69.4]

Item	Chemotherapy (n=16)	Chemotherapy combined with immunotherapy (n=17)	P-value
PR
No	13 (81.3%)	9 (52.9%)	0.176
Yes	3 (18.8%)	8 (47.1%)
SD
No	10 (62.5%)	12 (70.6%)	0.902
Yes	6 (37.5%)	5 (29.4%)
PD
No	9 (56.3%)	13 (76.5%)	0.389
Yes	7 (43.8%)	4 (23.5%)
DCR	9 (56.2%)	13 (76.4%)	0.282
ORR	3 (18.8%)	8 (47.1%)	0.176

Item	Chemotherapy (n=16)	Chemotherapy combined with immunotherapy (n=17)	P-value
PR
No	13 (81.3%)	9 (52.9%)	0.176
Yes	3 (18.8%)	8 (47.1%)
SD
No	10 (62.5%)	12 (70.6%)	0.902
Yes	6 (37.5%)	5 (29.4%)
PD
No	9 (56.3%)	13 (76.5%)	0.389
Yes	7 (43.8%)	4 (23.5%)
DCR	9 (56.2%)	13 (76.4%)	0.282
ORR	3 (18.8%)	8 (47.1%)	0.176

Item		No.	HR (Univariable)	HR (Multivariable)
Treatment	Chemotherapy	16 (48.5%)
	Chemotherapy combined with immunotherapy	17 (51.5%)	0.37 (0.17-0.80, P=0.012)	0.28 (0.11-0.70, P=0.007)
Gender	Male	19 (57.6%)
	Female	14 (42.4%)	1.76 (0.84-3.71, P=0.133)	1.34 (0.52-3.43, P=0.545)
Years		58.5 ± 8.6	0.99 (0.95-1.03, P=0.575)	0.97 (0.93-1.01, P=0.183)
Tumor type	Gallbladder cancer	11 (33.3%)
	Cholangiocarcinoma	22 (66.7%)	1.24 (0.59-2.59, P=0.574)	1.02 (0.46-2.26, P=0.970)
Tumor grade	Poorly differentiated	11 (33.3%)
	Moderately differentiated	22 (66.7%)	2.01 (0.88-4.62, P=0.100)	2.12 (0.82-5.49, P=0.121)
MSI	Stable	8 (24.2%)
	Unclear	25 (75.8%)	0.92 (0.40-2.08, P=0.834)	0.88 (0.37-2.13, P=0.784)