Abstract:
Objective To investigate the efficacy and safety of different transcatheter arterial chemoembolization (TACE)-based regimens in patients with unresectable hepatocellular carcinoma (uHCC) and explore the optimal timing for combining TACE with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).
Methods A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital, Southern Medical University. The patients were assigned into the following four groups according to different treatment regimens: TACE group (n=317), TACE combined with TKIs group (TACE+TKIs, n=66), TACE combined with ICIs group (TACE+ICIs, n=33), and TACE combined with TKIs+ICIs group (TACE+TKIs+ICIs, n=139). Subgroup analysis was performed within the TACE+TKIs+ICIs group, with patients being assigned into “pre-TACE” and “post-TACE” groups based on the timing of the combination therapy. Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors influencing overall survival (OS).
Results The TACE+TKIs+ICIs group showed the longest OS (21.9 months, 95% confidence interval CI: 17.2−26.6, P=0.030) and progression-free survival (PFS) (8.3 months, 95% CI: 7.3−9.3, P=0.004) compared to those in the other three groups. In the subgroup analysis, the “post-TACE” group had longer OS than the “pre-TACE” group (26.8 months vs. 19.2 months, P =0.011). The objective response rate (ORR) was 32.8%, 41.1%, 42.4%, and 52.5% (P=0.001) and the disease control rate (DCR) was 59.6%, 71.2%, 69.7%, and 82.7% (P<0.001) in the TACE, TACE+TKIs, TACE+ICIs, and TACE+TKIs+ICIs groups, respectively. The adverse events were similar to those reported in previous studies. Cox regression analysis revealed that tumor number, extrahepatic metastasis, and treatment regimen were independent factors influencing OS in patients (all P<0.05).
Conclusions TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE, and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes. The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.