This study aimed to assess the efficacy and safety of adjuvant transarterial chemoembolization (TACE) plus tyrosine kinase inhibitor (TKI) treatment in patients with hepatocellular carcinoma (HCC) with a high risk of early recurrence after curative resection.

Patients from multiple centres were divided into postoperative adjuvant TACE with (n=57) or without (n=142) TKI administration groups. The disease-free survival (DFS) curve was depicted by the Kaplan-Meier method, and the difference between the two groups was tested using the log rank test. Univariate and multivariate Cox analyses were performed to identify independent risk factors for DFS. Additionally, three propensity score analyses were performed to minimise the potential confounding factors to facilitate a more reliable conclusion. Adverse events (AEs) were assessed according to the Common Terminology Criteria for Adverse Events, version 4.0.

The 1-and 2-year DFS rates of the TACE plus TKI treatment group were 45.5% and 34.9%, respectively, which were significantly better than those of the TACE alone group (26.8% and 18.3%, respectively). Multivariate analysis identified adjuvant TACE plus TKI treatment as an independent prognostic factor for DFS (hazard ratio: 0.611, 95% confidence interval: 0.408-0.915, P=0.017). Further analysis based on the various propensity score methods yielded similar results. Subgroup analysis showed that patients with tumour diameter ≥5 cm, tumour number <3, absence of hepatic vein tumour thrombus and bile duct tumour thrombus, ruptured tumours, and stage IIIB could benefit more from TACE plus TKI treatment (all P<0.05). Some patients (33.33%) experienced grade ≥3 AEs in the TACE plus TKI group.

TACE plus TKI treatment can reduce the incidence of early recurrence with tolerable adverse events in HCC patients at high risk of recurrence after hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment.

This study aimed to compare the efficacy of transarterial chemoembolization (TACE) plus sorafenib (TACE-S) to TACE plus lenvatinib (TACE-L) for the treatment of HCC with portal vein tumor thrombus (PVTT).

This cohort study recruited patients from September 2017 to September 2020. A total of 59 and 57 consecutive patients were treated with TACE-L and TACE-S, respectively.

Before propensity score matching (PSM), comparing TACE-L to TACE-S, the median overall survival (OS) time was 16.4 months and 12.7 months, respectively [hazard ratio (HR) 1.34; 95% confidence interval (CI): 0.81-2.20; p = 0.25]. The median progression-free survival (PFS) time was 8.4 months and 7.43 months, respectively (HR 1.54; 95% CI: 0.98-2.41; p = 0.081). After PSM, the median OS time was 18.97 months and 10.77 months, respectively (HR 2.21; 95% CI: 1.12-4.38; p = 0.022); the median PFS time was 10.6 months (95% CI: 6.6-18.0 months) and 5.4 months (95% CI: 4.2-8.1 months), respectively (HR 2.62; 95% CI: 1.43-4.80; p = 0.002). After PSM, the overall response rate (ORR) was 66.8% vs. 33.3% [odds ratio (OR) 0.85; 1.05-6.90; p = 0.037].

Both TACE-L and TACE-S are safe, well-tolerated treatments for HCC with PVTT. In HCC with PVTT, TACE-L was significantly superior to TACE-S with respect to OS, PFS, and ORR. A larger-scale randomized clinical trial is needed.

The systemic treatment of hepatocellular carcinoma is changing rapidly. Three main classes of treatment are now available. Historically, multi-targeted tyrosine kinase inhibitors (TKIs) (sorafenib and lenvatinib as first-line; regorafenib and cabozantinib as second-line) were the first to show an improvement in overall survival (OS). Anti-vascular endothelial growth factor (anti-VEGF) antibodies can be used in first-line (bevacizumab) or second-line (ramucirumab) combination therapy. More recently, immuno-oncology (IO) has profoundly changed therapeutic algorithms, and the combination of atezolizumab-bevacizumab is now the first-line standard of care. Therefore, the place of TKIs needs to be redefined. The objective of this review was to define the place of TKIs in the therapeutic algorithm at the time of IO treatment in first-line therapy, with a special focus on lenvatinib that exhibits one of the higher anti-tumoral activity among TKI in HCC. We will discuss the place of lenvatinib in first line (especially if there is a contra-indication to IO) but also after failure of atezolizumab and bevacizumab. New opportunities for lenvatinib will also be presented, including the use at an earlier stage of the disease and combination with IOs.