Efficacy and safety of surufatinib and anti-PD-L1 therapy in combination with hepatic arterial infusion chemotherapy for unresectable intrahepatic cholangiocarcinoma

Abstract

BACKGROUND

The prognosis for unresectable intrahepatic cholangiocarcinoma (ICC) is poor, and the efficacy of conventional chemotherapy remains unsatisfactory. Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) has demonstrated activity in patients with unresectable ICC. Surufatinib is a small-molecule antiangiogenic tyrosine kinase inhibitor approved in China for second-line treatment of advanced cholangiocarcinoma.

AIM

To evaluate the preliminary clinical efficacy and safety of surufatinib plus anti- programmed death-ligand 1 (PD-L1) therapy in conjunction with FOLFOX-HAIC among individuals diagnosed with treatment-naive, surgically inoperable ICC.

METHODS

Between August 2023 and July 2025, patients with unresectable ICC who initially received surufatinib plus anti-PD-L1 therapy in conjunction with FOLFOX-HAIC were reviewed for study inclusion. Efficacy was determined based on tumor response and survival outcomes, while the safety profile was evaluated based on the incidence of principal adverse events (AEs).

RESULTS

Forty eligible patients were enrolled in this study. Among the 36 patients evaluable for efficacy, the objective response rate based on Response Evaluation Criteria in Solid Tumors version 1.1 criteria was 47.2%. The 6-month, 12-month, and 24-month overall survival rates were 82.5%, 63.3%, and 55.4%, respectively. The median progression-free survival was 6.3 months (95% confidence interval: 5.7-6.9). Notably, 22.5% (9/40) of patients underwent radical surgical resection following successful conversion. All patients (100.0%) experienced AEs, while 30.0% (12/40) developed grade 3 or 4 AEs.

CONCLUSION

The combination of FOLFOX-HAIC, surufatinib, and anti-PD-L1 therapy demonstrated substantial clinical efficacy alongside a favorable safety profile among patients with previously untreated and unresectable ICC. This therapeutic strategy could represent an alternative treatment option for selected patients.

Keywords: Unresectable intrahepatic cholangiocarcinoma; Surufatinib; Anti-programmed cell death-ligand 1; Hepatic arterial infusion chemotherapy; 5-Fluorouracil

Core Tip: Combining surufatinib and anti-programmed death-ligand 1 therapy with hepatic arterial infusion chemotherapy yields promising antitumor activity and survival benefits for unresectable intrahepatic cholangiocarcinoma. This innovative regimen demonstrates a highly favorable safety profile, characterized by a low incidence of grade 3 or 4 adverse events. Notably, patients who respond to this combination therapy achieve significantly better prognostic outcomes compared to non-responders. These findings highlight a potent, well-tolerated therapeutic strategy that could substantially improve clinical management for unresectable intrahepatic cholangiocarcinoma.