Abstract
A deteriorated liver functional reserve during systemic therapy for unresectable hepatocellular carcinoma (HCC) causes poor patient outcomes. We aimed to identify predictive factors associated with the deterioration of Child-Pugh score at 8 weeks after lenvatinib initiation. Patients with adequate clinical data and baseline preserved serum samples available were included. Baseline fibroblast growth factor (FGF)19 and 21, angiopoietin (ANG)2, and vascular endothelial growth factor (VEGF) levels were evaluated. Thirty-seven patients were included, and 6, 15, 14, and 2 experienced complete response, partial response, stable disease, and progressive disease, respectively. Twenty-four (65%) and 13 (35%) patients showed a maintained/improved and deteriorated Child-Pugh-score, respectively. While baseline clinical data, treatment response, and laboratory data were similar between these two patient groups, baseline ANG2 and VEGF levels were significantly higher (P = 0.0017) and lower (P = 0.0231), respectively, in patients with deteriorated Child-Pugh score than in those without. Based on receiver operating characteristic curve analysis, cut-off values for ANG2 and VEGF were found to be 3,108 pg/mL and 514.9 pg/mL, respectively. Among patients with low VEGF and high ANG2, 89% (8/9) exhibited a deteriorated Child-Pugh score, whereas none of the patients (0/9) with high VEGF and low ANG2 did. The deterioration of the Child-Pugh score in patients with unresectable HCC who are treated with lenvatinib may be predictable based on combined baseline serum ANG2 and VEGF levels.
Highlights
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide [1]
As various clinical trials on novel systemic therapies for unresectable HCC could not demonstrate significant efficacy of multikinase inhibitors, including sunitinib, brivanib, and linifanib, or even report non-inferiority compared to sorafenib [2,3,4], systemic therapy is limited to sorafenib alone [5]
Another multikinase inhibitor, regorafenib [6], and a monoclonal antibody targeting vascular endothelial growth factor receptor (VEGFR) 2, ramucirumab [7], have been approved as second-line systemic therapies, whereas the multikinase inhibitor lenvatinib [8] has been approved as firstline systemic therapy for patients with advanced HCC
Summary
Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide [1]. As various clinical trials on novel systemic therapies for unresectable HCC could not demonstrate significant efficacy of multikinase inhibitors, including sunitinib, brivanib, and linifanib, or even report non-inferiority compared to sorafenib [2,3,4], systemic therapy is limited to sorafenib alone [5]. This limited therapeutic option might contribute to the poor prognosis of patients with advanced HCC. Most of these patients have a deteriorated liver functional reserve due to chronic liver disease, such as hepatitis C or B virus infection or nonalcoholic steatohepatitis, affecting their prognosis [10] and limiting their therapeutic options
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
