Clinical outcomes of hepatic arterial infusion chemotherapy combined with tyrosine kinase inhibitors and anti-PD-1 immunotherapy for unresectable intrahepatic cholangiocarcinoma

Objective To compare the treatment efficacy and safety of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death 1 (PD-1) immunotherapy combined with transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). Methods Patients with unresectable ICC received TKIs and anti-PD-1 immunotherapy combined with HAIC (HTP group) or TACE (TTP group) were included. The clinicopathological characteristics, treatment efficacy, and adverse events (AEs) were compared between the two groups. The factors associated with response rate to the treatments were evaluated. Results A total of 58 patients were enrolled, with 39 in the HTP group and 19 in the TTP group. Patients in the HTP group exhibited a better objective response rate (ORR; Response Evaluation Criteria in Solid Tumors [RECIST] 48.7% vs 15.8%, P = 0.02; modified RECIST [mRECIST] 61.5% vs 21.1%, P = 0.004) and disease control rate (DCR; 82.1% vs 36.8%, P = 0.001) compared to the TTP group. The median progression-free survival (PFS) rate was not reached and the 1-year PFS rate was 61.9% in the HTP group, whereas the median PFS was 11.0 months and the 1-year PFS rate was 31.6% in the TTP group. The type of treatment and tumor size were significant factors for the response rate. More patients in the HTP group presented rash, abdominal pain and hand-foot syndrome, but all AEs were relieved after symptomatic treatment, and no treatment-related death occurred. Conclusions For unresectable ICC, treatment with a combination of HAIC with TKIs and anti-PD-1 immunotherapy was effective and safe. Tumor size might serve as a significant factor for the response rate following treatment for unresectable ICC.