Real-World Effectiveness of Sorafenib versus Lenvatinib Combined with PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma

Abstract

Immune checkpoint inhibitors (ICIs) combined with multitarget tyrosine kinase inhibitors (MTKIs) exert a synergistic effect and are effective in unresectable hepatocellular carcinoma (uHCC). However, precise data regarding the real-world clinical applications of these combination therapies in uHCC are lacking. This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a clinical setting. Among 208 patients with uHCC treated with PD-1 inhibitors, 88 were administered with ICIs in combination with sorafenib or lenvatinib. The treatment response and survival outcomes were evaluated. Predictors of survival were assessed by multivariate analysis. A total of 49 patients were treated with PD-1 inhibitors combined with sorafenib, and 39 patients were treated with PD-1 inhibitors combined with lenvatinib. The lenvatinib group exhibited a stronger objective response rate (ORR) (20.51% vs. 16.33%) and had a higher disease control rate (41.03% vs. 28.57%) than did the sorafenib group. The median overall survival was longer in the lenvatinib group than the sorafenib group (13.1 vs. 7.8 months; hazard ratio = 0.39, p = 0.017). The incidence of treatment-related adverse events was similar. PD-1 inhibitors combined with lenvatinib can be a feasible treatment strategy for HCC patients receiving MTKI-based combination therapy. PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Additional larger-scale and prospective studies should be conducted to verify the study results.

Biomimetic Responsive Nanoconverters with Immune Checkpoint Blockade Plus Antiangiogenesis for Advanced Hepatocellular Carcinoma Treatment

“…First, patient eligibility is restricted with only those meeting the current inclusion criteria (limited to cases with a Child–Pugh A score) being considered, primarily because of the occurrence of severe immune-related adverse events resulting from the long half-life and off-target effects of mAbs. , Second, the high cost of treatment is rooted in the complexity of mAb production. , Consequently, recent clinical studies have shown a growing inclination toward the incorporation of more cost-effective small-molecule inhibitors. Thus, the combination of small-molecule TKIs with antiangiogenesis properties, such as apatinib (Apa), regorafenib, or lenvatinib, with mAb targeting of PD-1/PD-L1, has displayed enhanced antitumor efficacy in clinical trials for treating advanced HCC. − Certainly, the contrasting physicochemical properties inherent to these two types of drugs produce distinct pharmacokinetic profiles. Consequently, when employed concurrently, this divergence in their pharmacokinetics may result in a notable delay in achieving the desired therapeutic effectiveness.…”