Abstract
Triple therapy of hepatic arterial infusion chemotherapy (HAIC) combined with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) achieves satisfactory clinical efficacy in advanced hepatocellular carcinoma (HCC). However, the optimal therapeutic strategy to improve prognosis in this patient population remains controversial. The objective of this retrospective study was to evaluate the efficacy and safety of HAIC-based therapy, either sequentially (SE) or concurrently (Con) combined with targeted immunotherapy, in patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC. This retrospective study analyzed 235 patients with advanced HCC who received FOLFOX-based HAIC in combination with ICIs and TKIs either concurrently or sequentially at the Affiliated Hospital of North Sichuan Medical College from January 2020 to December 2024. Propensity score matching (PSM) was performed at a 1:1 ratio to eliminate potential imbalances in confounding factors. Patients were categorized into the sequential group (SE) and concurrent group (Con) based on whether the interval between the completion of HAIC and the initiation of systemic therapy exceeded three weeks. Following PSM, each group contained 85 patients. Statistical comparisons of Overall Survival (OS) (via Kaplan-Meier and log-rank tests) revealed a significantly longer median survival in the Con group (14.5 months) versus the SE group (11.2 months, P < 0.01). Furthermore, the median Progression-Free survival (PFS) in the Con group (7.9 months) was also longer than that in the SE group (6.2 months). Treatment responses and adverse events (AEs) profiles were documented. Upon analysis according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), the objective response rate (ORR) of the SE regimen was lower than that of the Con regimen. The Con group had a generally higher AE incidence, with significantly higher rates of hyperbilirubinemia (44.7% vs. 24.7%, p = 0.04 < 0.05) and anemia (43.5% vs. 16.5%, p = 0.005 < 0.05) than the SE group. No grade 5 severe and life-threatening AEs were reported in either group.