Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib

Background: Hepatocellular 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 methods: We 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. Results: Among 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). Conclusion: NASH 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

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

Background: Lenvatinib is approved as the 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 multicenter cohort (ELEVATOR) from Germany and Austria. Methods: We conducted a retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites. Overall survival, progression-free survival, overall response rate, and adverse event rates were assessed and analyzed. Results: Pa- tients receiving lenvatinib in the real-world setting reached a median overall survival (mOS) of 12.8 months, which was comparable to the results reported from the REFLECT study. mOS and median progression-free survival (mPFS) were 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, hazard ratio [HR] 0.55, 95% confidence interval [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 and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as a meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC. (C) 2022 The Author(s). Published by S. Karger AG, Base

Real-world data for Lenvatinib in hepatocellular carcinoma (ELEVATOR)

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 $\geq$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 $\geq$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