Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study

Abstract

Background: The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. The authors aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC greater than 7.0 cm accompanied with major PVTT.

Materials and methods: This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score matching (PSM).

Results: A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524).

Conclusion: The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

Trial registration: ClinicalTrials.gov NCT06265883.

Figure 1

Flowchart of the study. HAIC, hepatic arterial infusion chemotherapy; HCC, hepatocellular carcinoma; Len+DEB-TACE, lenvatinib plus drug-eluting bead transarterial chemoembolization; Len+DEB-TACE+HAIC, lenvatinib plus drug-eluting bead transarterial chemoembolization and hepatic arterial infusion chemotherapy; PVTT, portal vein tumor thrombosis; TACE, transarterial chemoembolization.

Figure 2

A 44-year-old man with huge hepatocellular carcinoma and Vp4 portal vein tumor thrombosis (PVTT) who received lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC). (A) Pretreatment contrast-enhanced computed tomography (CT) demonstrated an intrahepatic mass of 11.8 cm in the right lobe (arrows) with Vp4 PVTT (arrowheads). (B) Digital-subtraction angiography (DSA) before embolization showed the tumor-feeding vessels derived from right hepatic artery (arrow). (C) DSA after the first DEB-TACE showed that the tumor blush remained but significantly reduced, and the microcatheter was reserved at the right hepatic artery for HAIC (arrow); (D) Contrast-enhanced CT image obtained 2 months after three DEB-TACE and HAIC treatments demonstrated remarkable tumor shrinkage without enhancement inside the intrahepatic tumor and PVTT (arrow), with patency of the main trunk and left branches of portal vein (arrowheads).

Figure 3

Kaplan–Meier curves for time to progression (TTP) and overall survival (OS) of the patients in matched cohorts according to treatment modality. (A) TTP of overall tumor. (B) TTP of intrahepatic tumor. (C) TTP of portal vein tumor thrombosis. (D) OS. Len+DEB-TACE, lenvatinib plus drug-eluting bead transarterial chemoembolization; Len+DEB-TACE+HAIC, lenvatinib plus drug-eluting bead transarterial chemoembolization and hepatic arterial infusion chemotherapy.

Figure 4

Subgroup analyses of time to progression (A) and overall survival (B). ALBI, albumin-bilirubin; ECOG PS, Eastern Cooperative Oncology Group performance status; HBsAg, hepatitis B surface antigen; HR, hazard ratio; Len+DEB-TACE, lenvatinib plus drug-eluting bead transarterial chemoembolization; Len+DEB-TACE+HAIC, lenvatinib plus drug-eluting bead transarterial chemoembolization and hepatic arterial infusion chemotherapy; PVTT, portal vein tumor thrombosis.