Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma

Abstract

BackgroundLenvatinib combined with programmed cell death protein-1 (PD-1) inhibitors has resulted in good survival outcomes in the treatment of unresectable hepatocellular carcinoma (HCC). Hepatic artery infusion chemotherapy (HAIC) has also attracted attention due to its high response rates and favorable survival for advanced HCC patients. The present study aimed to compare the efficacy of HAIC combined with PD-1 inhibitors plus lenvatinib (HPL) and PD-1 inhibitors plus lenvatinib (PL) in patients with advanced HCC.MethodsBetween July 2018 and December 2019, patients diagnosed with advanced HCC who initially received HPL or PL treatment were reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.ResultsIn total, 70 patients met the criteria and were included in the present study, and they were divided into the HPL group (n = 45) and PL group (n = 25). The overall response rate (40.0 vs. 16.0%, respectively; p = 0.038) and disease control rate (77.6 vs. 44.0%, respectively; p < 0.001) were higher in the HPL group than in the PL group. The median overall survival was 15.9 months in the HPL group and 8.6 months in the PL group (p = 0.0015; HR = 0.6; 95% CI 0.43–0.83). The median progression-free survival was 8.8 months in the HPL group and 5.4 months in the PL group (p = 0.0320; HR = 0.74; 95% CI 0.55–0.98).ConclusionCompared to PL, HPL was associated with a significantly better treatment response and survival benefits for patients with advanced HCC.

Pembrolizumab plus lenvatinib with or without hepatic arterial infusion chemotherapy in selected populations of patients with treatment-naive unresectable hepatocellular carcinoma exhibiting PD-L1 staining: a multicenter retrospective study

“…The findings of the present study are broadly consistent with a retrospective study [ 2 ] of 70 patients with advanced HCC that assessed the antitumour efficacy of HAIC combined with PD-1 inhibitors plus lenvatinib in patients with advanced HCC. In the retrospective review, the median OS (15.9 vs. 8.6 months, respectively; HR 0.60, 95% CI, 0.43–0.83; p = 0.0015) and median PFS (8.8 vs. 5.4 months, respectively; HR 0.74, 95% CI, 0.55–0.98; p = 0.0320) were higher in the HAIC plus PD-1 inhibitors plus lenvatinib group compared with the PD-1 inhibitors plus lenvatinib group.…”

“…Accordingly, hepatic lesion control is conducive to improving prognosis to a certain extent [ 11 ]. Although the efficacy of the pembrolizumab plus lenvatinib regimen in extending survival is encouraging [ 16 ], distinct differences have been detected in the duration of HAIC therapy [ 2 ]. Management of advanced uHCC by inhibiting or blocking the activation of tumour signal transduction pathways is a strategy to address malignant tumours, and it may represent a trend [ 8 , 25 , 26 ].…”

“…Lenvatinib inhibits the kinase activities of vascular endothelial growth factor receptors that are associated with pathogenic angiogenesis and tumour growth [ 16 ]. Lenvatinib indirectly decreases the number of total PD-1 receptors by reducing the number of cancer cells, reinforcing the effect of pembrolizumab by promoting cancer cells to enter into “a dormant state” [ 2 , 15 ]. This synergistic effect of pembrolizumab and lenvatinib may represent the basis for HAIC’s effectiveness in managing advanced HCC.…”

“…Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers and is the 4th leading cause of cancer-related death [ 1 ]. In China, HCC is primarily attributed to chronic inflammation resulting from hepatitis B virus infection [ 2 ]. Most patients are newly diagnosed with unresectable disease.…”

“…Most patients are newly diagnosed with unresectable disease. Thus, treatment options are limited, and the prognosis is poor [ 2 , 3 ]. The management of uHCC with inherent “immune escape” remains controversial [ 3 , 4 ].…”