Transarterial chemoembolization combined with molecular targeted agents plus immune checkpoint inhibitors for unresectable hepatocellular carcinoma beyond the up-to-seven criteria: a propensity score-matching analysis

Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria. Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs). There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, <i>p</i> = 0.007; PFS: 15.4 months vs. 4.8 months, <i>p</i> &lt; 0.001). The objective response rate (ORR) in the TACE-MTAs-ICIs group was higher than that in the TACE group (65.1% vs. 37.2%, <i>p</i> = 0.010). Reversible AEs (grade 3 or 4) occurred differently in TACE-MTAs-ICIs and TACE groups (83.7% vs. 51.2%, <i>p</i> = 0.001). Univariate and multivariate analyses revealed that TACE-MTAs-ICIs treatment was an independent favourable prognostic factor for both PFS and OS (<i>p</i> &lt; 0.001). For uHCC patients beyond the up-to-seven criteria, TACE-MTAs-ICIs provided superior ORR and OS. Early combined TACE and systemic treatment should shift for patients who are beyond these criteria. The ORR and median OS reached 65.1% and 27.2 months, respectively, in the treatment model of TACE-MTAs-ICIs for patients with unresectable HCC that were beyond the up-to-seven criteria.TACE-TKI-ICI yielded a synergistic effect on these patients and was an independent favourable prognostic factor for PFS and OS. The ORR and median OS reached 65.1% and 27.2 months, respectively, in the treatment model of TACE-MTAs-ICIs for patients with unresectable HCC that were beyond the up-to-seven criteria. TACE-TKI-ICI yielded a synergistic effect on these patients and was an independent favourable prognostic factor for PFS and OS.