Abstract
BackgroundHepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes.Patients and methodsWe conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed.ResultsAmong the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin–bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047).ConclusionNASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients.
Highlights
Hepatocellular carcinoma (HCC) treatment constitutes a big challenge in the field of oncology, due to the complexity of its pathogenesis and the heterogeneity of etiology
In the univariate analysis for progression-free survival (PFS) nonalcoholic steatohepatitis (NASH)-HCC was associated with longer median progression-free survival (mPFS) (7.5 versus 6.5 months; hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.71-0.99; P 1⁄4 0.0436)
In the univariate analysis for overall survival (OS) NASH-HCC was associated with longer median overall survival (mOS) [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P 1⁄4 0.0006; Figure 1A]
Summary
Hepatocellular carcinoma (HCC) treatment constitutes a big challenge in the field of oncology, due to the complexity of its pathogenesis and the heterogeneity of etiology. The results of the REFLECT trial confirmed the noninferiority in terms of overall survival (OS) of another multikinase inhibitor lenvatinib compared with sorafenib[9]; but demonstrated a superiority in terms of progression-free survival (PFS).[9] the REFLECT trial highlighted similar baseline scores on the European Organisation for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ)-C30 and EORTC QLQ-HCC18 health questionnaires in the two arms, but analysis of time to clinically meaningful deterioration showed that role functioning, pain and diarrhea were experienced earlier in the group of patients treated with sorafenib compared with those receiving lenvatinib.[9] Besides multikinase inhibitors, in the past years another class of drug has been introduced in the advanced HCC setting armamentarium: immunotherapy. In the univariate analysis for OS NASHHCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P 1⁄4
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