Lenvatinib for the treatment of hepatocellular carcinoma—a real-world multicenter Australian cohort study

Abstract

Introduction Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. Methods We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. Results A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59–75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8–14.0) and 5.3 months (95% CI: 2.8–9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child–Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). Conclusions Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

The New Era of Systemic Treatment for Hepatocellular Carcinoma: From the First Line to the Optimal Sequence

“…In a meta-analysis addressing the use of Sorafenib in Child-Pugh B patients with advanced HCC, the median OS result was significantly worse than that of patients with a good liver function (4.6 vs. 8.8 months) [79]. Similar results have been obtained for Lenvatinib in a multicenter cohort study: 108 patients with Child-Pugh A, 27 with Child-Pugh B and 2 with Child-Pugh C were treated and the median OS was 12.5 months in those with preserved liver function vs. 5.6 months in those with decompensated liver function [80]. Regarding ICIs, Nivolumab as a monotherapy has been studied in cohort 5 of the CheckMate 040 trial, in patients with advanced HCC and Child-Pugh B: it demonstrated clinical activity (median OS of 7.6 months and 55% of response rate), with a favorable safety, thus suggesting it could be a potential treatment option for patients with Child-Pugh B liver function [81].…”

Real-world efficacy and prognostic factors of lenvatinib plus PD-1 inhibitors in 378 unresectable hepatocellular carcinoma patients

“…Patients with uHCC treated with systematic therapy exhibit a median overall survival (OS) of only 11.8-21.2 months based on both phase III studies [3][4][5][6][7][8][9][10] and real-world studies [11][12][13][14].…”

A Case of Tracheoesophageal Fistula in a Non-metastatic Site During Lenvatinib Treatment for Hepatocellular Carcinoma

“…Lenvatinib is a multitargeted tyrosine kinase inhibitor that inhibits the vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, and platelet-derived growth factor receptors, RET, and KIT (5), and cause several adverse events including hypertension, diarrhea, anorexia, hand-foot skin reaction, and hypothyroidism (6). Although gastrointestinal perforation or fistula formation during lenvatinib therapy has been reported as a serious adverse effect (7,8), all reports of TEF associated with lenvatinib are for tracheoesophageal invasion of thyroid cancer (2,3). The etiology of lenvatinib-associated gastrointestinal perforation or fistula is thought to be because the inhibitory effect of lenvatinib on angiogenesis may damage the structure and function of gastrointestinal vessels (9), induce arterial thromboembolism (10), and inhibit the healing of gastrointestinal ulcers and colonic diverticulitis, which in turn may lead to perforation (11).…”