Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as a first-line treatment for unresectable intrahepatic cholangiocarcinoma: a propensity score matching analysis.

Abstract

Background: Given the limited efficacy of current first-line therapies, there is an urgent need to develop novel treatment strategies to improve the prognosis of patients with unresectable intrahepatic cholangiocarcinoma (uICC). This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) regimens (HAIC-FO) plus anti-programmed death-(ligand) 1 immunotherapy [αPD-(L)1] antibody [HAIC+αPD-(L)1] compared to systemic chemotherapy (SYS) plus αPD-(L)1 antibody [SYS+αPD-(L)1] as a first-line treatment for patients with uICC.

Methods: In this retrospective study, treatment-naive uICC patients who were treated with HAIC+αPD-(L)1 or SYS+αPD-(L)1 were included. The clinical characteristics, therapeutic outcomes, and adverse events (AEs) of the patients in the two groups were compared. Propensity score matching (PSM) was performed to minimize biases between groups.

Results: From January 2019 to January 2023, a total of 182 patients were enrolled; 147 patients were included in the HAIC+αPD-(L)1 group and 35 patients were included in the SYS+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SYS+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group had longer median overall survival (mOS), median progression-free survival (mPFS), and median intrahepatic PFS (mIPFS) than did the SYS+αPD-(L)1 group (mOS: 14.5 vs. 10.5 months, P=0.02; mPFS: 10.4 vs. 6.4 months, P=0.02; mIPFS: 11.4 vs. 6.5 months, P<0.001). The overall incidence of AEs was comparable between the two groups, but the HAIC+αPD-(L)1 group had a lower incidence of grade 3-4 AEs related to anemia, leukopenia, weight loss, and fatigue.

Conclusions: HAIC+αPD-(L)1 had acceptable toxic effects and might improve outcomes compared to SYS+αPD-(L)1 as a first-line treatment for patients with uICC.