Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study

Abstract

Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Atezolizumab Plus Bevacizumab in Patients with Advanced and Progressing Hepatocellular Carcinoma: Retrospective Multicenter Experience

“…This is consistent with recently published data on the use of atezolizumab plus bevacizumab [ 21 ] in first-line treatment. Nevertheless, multivariate Cox regression identified liver function (ALBI score) as the strongest prognostic marker in our cohort, underscoring the known effect of liver function in determining prognosis in these patients [ 22 , 23 ].…”

Lenvatinib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

“…This proves that lenvatinib can still provide a favorable efficacy, even for patients who do not meet the REFLECT criteria. A similar result was also demonstrated in patients with advanced HCC in the study of Welland et al [ 38 ], despite the fact that some surgically treated patients were included. When lenvatinib was compared with sorafenib, unlike the previous phase III clinical trial that showed no significant difference in OS, our meta-analysis showed that lenvatinib could significantly improve OS and PFS and offer better ORR and DCR.…”

LINC01468 drives NAFLD-HCC progression through CUL4A-linked degradation of SHIP2

“…Therefore, we assessed the effects of LINC01468 on lenvatinib (LVB) and sorafenib (SOR) sensitivity. Sorafenib was the first multi-tyrosine kinase inhibitor approved for the treatment of patients with unresectable HCC [ 25 ], while lenvatinib is another tyrosine kinase inhibitor that received approval for first-line treatment of patients with advanced HCC [ 26 ]. LINC01468 silencing sensitized SNU-449 cells to LVB, as reflected by a reduction in cell viability (Fig.…”