Efficacy and safety of transarterial chemoembolization with chemotherapy, PD-1/PD-L1 inhibitors, and tyrosine kinase inhibitors in unresectable intrahepatic cholangiocarcinoma

Abstract

Background: Chemotherapy, targeted therapy, and immunotherapy have all been shown to achieve some efficacy in treating intrahepatic cholangiocarcinoma (ICC). However, these systemic treatments have not provided optimal results for some patients. Therefore, the combination of transarterial chemoembolization (TACE) and hepatic artery infusion chemotherapy or other local interventional therapy methods is being considered for the treatment of liver tumors.

Aim: To evaluate the efficacy and safety of combining chemotherapy, targeted therapy, and immunotherapy, with or without TACE, in patients with ICC.

Methods: We recruited 83 patients with unresectable ICC from July 2021 to December 2023 at the Affiliated Hospital of Xuzhou Medical University. Forty-one patients received TACE combined with chemotherapy, tyrosine kinase inhibitors, and programmed death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors (experimental group), whereas 42 patients were treated with chemotherapy, tyrosine kinase inhibitors, and PD-1/PD-L1 inhibitors (control group). Short-term efficacy was assessed using the modified response evaluation criterion, and the objective response rate, disease control rate, progression-free survival, and incidence of adverse events were compared between groups.

Results: The objective response rate in the experimental group was greater than that in the control group (39.0% vs 19.0%, P < 0.05). The disease control rate in the experimental group was significantly greater than that in the control group (75.6% vs 52.4%, P < 0.05). The median progression-free survival times were 14.3 months in the experimental group and 12.7 months in the control group (P < 0.05). All 41 patients in the experimental group developed postembolization syndrome. Among the symptoms, fever and pain were significantly more common in the experimental group than in the control group (85.4% vs 11.9%, P < 0.001 and 58.5% vs 9.5%, P < 0.001). No grade 4 or 5 treatment-related adverse events were observed in either group.

Conclusion: In patients with unresectable ICC, TACE combined with chemotherapy, tyrosine kinase inhibitors, and PD-1/PD-L1 inhibitors has good efficacy and high safety, indicating potential benefits for these patients.

Keywords: Efficacy; Intrahepatic cholangiocarcinoma; Programmed death 1/programmed cell death ligand 1 inhibitors; Transarterial chemoembolization; Tyrosine kinase inhibitors.

Figure 1

Comparison of progression-free survival between the experimental and control groups. The experimental group received transarterial chemoembolization combined with chemotherapy, tyrosine kinase inhibitors, and programmed death 1/programmed cell death ligand 1 inhibitors, while the control group received chemotherapy, tyrosine kinase inhibitors, and programmed death 1/programmed cell death ligand 1 inhibitors without transarterial chemoembolization. The number of patients at risk at different time points is shown below the horizontal axis.