Efficacy and safety of lenvatinib monotreatment and lenvatinib-based combination therapy for patients with unresectable hepatocellular carcinoma: a retrospective, real-world study in China

Abstract

Background Lenvatinib and lenvatinib-based combination treatments are widely used in patients with unresectable hepatocellular carcinoma (uHCC) in clinical practice, but their curative effect and safety need further study in the real world. Methods This was a retrospective study involving patients with uHCC receiving lenvatinib monotherapy and lenvatinib-based combination treatment between Nov, 2018 and Sep, 2020 in Nanfang Hospital. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), time to tumor progression (TTP), and overall survival (OS). Treatment-related adverse events (TRAEs) were recorded and graded. Efficacy and safety of monotherapy and combination therapy were compared. Stratified analysis was performed according to systemic line of treatment and medication regimen for combination therapy. Results For lenvatinib monotherapy (n = 39), OS and PFS were 80 weeks and 24.3 weeks, respectively. For combination treatment (n = 72), median OS and PFS were 99 weeks and 45.6 weeks, respectively. OS, PFS, and TTP for patients in the combination treatment cohort were significantly longer compared to those of patients in the monotreatment cohort (OS: P = 0.04, PFS: P = 0.003; TTP, P = 0.005). The incidence of TRAEs could be controlled both in the monotherapy cohort and the combination treatment cohort. In the monotherapy cohort, OS and PFS were significantly decreased in the second-line treatment group compared with the first-line treatment group, while no differences were observed in the combination cohort. The efficacy of triple therapy (lenvatinib plus PD-1 antibody plus TACE or HAIF) was similar to lenvatinib plus PD-1 antibody or lenvatinib plus TACE or HAIF. Conclusions Our real-world study showed that lenvatinib monotherapy and lenvatinib-based combination therapy were well tolerated, with encouraging efficacies in patients with uHCC. Lenvatinib-based combination therapy showed a better curative effect compared with lenvatinib single-agent therapy. In patients who have failed first-line TKI treatment, lenvatinib-based combination therapy may be a better choice than lenvatinib single-agent therapy. Lenvatinib-based triple therapy may not have an advantage over dual therapy.

Efficacy and Safety of Lenvatinib Combined With PD-1 Inhibitors Plus TACE for Unresectable Hepatocellular Carcinoma Patients in China Real-World

“…This might be the cause of the result. In addition, compared with other studies in the literature, the PFS of lenvatinib-TACE was 5.5 -11.6 months (30)(31)(32), while the PFS of our LePD1-TACE triple treatment achieved 10.4 months, our results were in the upper range. Notably, the different results between these studies and our data should be viewed with caution.…”

“…Secondly, our study was a singlearm design and was limited by the lack of a control group. Zhu et al (31) reported that the effectiveness of triple therapy (Lenvatinib + PD-1 inhibitors + TACE or HAIC) is not superior to dual therapy (Lenvatinib + PD-1 inhibitors or Lenvatinib + TACE or HAIC). Therefore, multicenter randomized controlled clinical trials need to be carried out to verify the efficacy and safety of different combinations.…”

Feasibility and Tolerability of Lenvatinib, Plus PD-1 Blockades for Patients with Unresectable Hepatocellular Carcinoma: A Retrospective Exploratory Study

“…It seemed that patients with advanced HCC might benefited from lenvatinib plus PD-1 blockades administration uniformly regardless of the majority baseline characteristic subgroups, which was basically consistent with a previous study initiated by Zhu et al that investigated the efficacy of lenvatinib monotherapy and lenvatinib-based combination therapy for patients with unresectable HCC. 31 The exploratory analysis demonstrated that almost all the baseline characteristic subgroups might benefit from lenvatinib and lenvatinib-based combination administration. These conclusions highlighted that the effectiveness of lenvatinib plus PD-1 blockades was stable and balanced.…”

Real-World Study: A Powerful Tool for Malignant Tumor Research in General Surgery

“…A multicenter analysis in Korea also confirmed that lenvatinib has a good curative effect on aHCC patients, and the treatment is well tolerated by patients [ 55 ]. Further studies have found that for patients with uHCC, lenvatinib-based combination therapy (lenvatinib plus PD-1 antibody plus transcatheter arterial chemoembolization (TACE) or hepatic arterial infusion with drug filtration (HAIF), lenvatinib plus PD-1 antibody, lenvatinib plus TACE or HAIF) is more effective than lenvatinib monotherapy [ 56 ]. When uHCC patients become resistant to lenvatinib, sorafenib as a second-line treatment may be effective and may not worsen the liver reserve [ 57 ].…”