Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study

Abstract

Purpose In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan–Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results Median follow-up duration was 18 (4.0–26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8–30.5) months, whereas the median PFS was 14.5 (range, 1.3–27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitors for advanced hepatocellular carcinoma with macrovascular invasion

“…The objective response rates were 2%, 24.1%, and 27.3% for sorafenib, lenvatinib, and atezolizumab plus bevacizumab group; Progression-free survival for sorafenib was 7.4 months, and 6.8 months for Atezolizumab plus Bevacizumab; The median overall survival was 10.7 months for sorafenib, 13.6 months for lenvatinib, 19.2 for Atezolizumab plus bevacizumab [ 13 , 19 , 21 , 46 ]. However, the main subgroup in a study was Vp4 PVTT, the PFS was 4.9 months, the OS was 9.4 months, and the objective response rate of PVTT based on mRECIST was 61.5% who received PD-1 inhibitor lenvatinib plus radiotherapy in previous study [ 47 ]; The intrahepatic tumor objective response rate was 68.3%, and the median OS, PFS was 21.7 months and 14.5 months for patients with main trunk portal vein tumor thrombus who received transarterial chemoembolization plus lenvatinib and PD-1 inhibitors [ 48 ]. The high ORR observed in patients receiving HAIC, lenvatinib, and PD-1 antibodies may be due to the synergistic antitumor effects of HAIC, lenvatinib, and PD-1 inhibitors.…”

Proton Beam Therapy for Treating Patients with Hepatocellular Carcinoma with Major Portal Vein Tumor Invasion: A Single Center Retrospective Study

“…Moreover, it is likely that the use of PBT in combination with agents such as lenvatinib will improve treatment outcomes. In recent years, several clinical trials have been conducted and reported on the combination of immune checkpoint inhibitors and PBT for HCC [ 48 , 49 ]. In Japan, several clinical trials and prospective studies of PBT for HCC have been conducted.…”