Effects of disease aetiology on outcomes for unresectable HCC treated with lenvatanib or atezobev: A real world retrospective study.
Authors: Dominelli Whiteley Nick , Evans Jeff , Naylor Gregory 
Published: January 2025

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Background:
Hepatocellular Carcinoma (HCC) is the most common primary liver cancer and a leading cause of cancer-death worldwide.
1
Standard of care first line treatment for unresectable HCC is Atezolizumab plus Bevacizumab (AtezoBev)
1
while the multi-kinase inhibitor Lenvatinib
2
is also available in the first line setting. No randomised studies have compared these treatments directly. Real world data suggests similar overall survival (OS) with AtezoBev possibly superior in patients with a viral hepatitis aetiology and Lenvatinib superior in NAFLD.
3,4,5,6,7
Methods:
We evaluated patients treated with Lenvatinib or AtezoBev in a retrospective cohort of patients who commenced first-line treatment in the West of Scotland from 04/12/2015 to 28/11/2023. 102 received Lenvatinib and 52 AtezoBev. We collected data on progression free survival (PFS), OS, demographics and disease aetiology- classified primarily as viral hepatitis, acholic liver disease (ALD) or NAFLD.
Results:
AtezoBev patients had improved mOS compared with Lenvatinib (13.8 vs 9. 1 months,
p
= 0.04). No statistically significant differences were observed in mPFS (5.5 vs 3.5 months,
p
= 0.31). Of the three aetiologies considered, the only statistically significant (p<0.05) difference between the treatments was OS in the NAFLD group (24.1 vs 9.1 months,
p
= 0.04). When considering patient demographic and disease factors, Child-Pugh score was most significant. Patients with Childs=5 liver disease had much longer OS and PFS compared with Childs≥6 disease. Similarly, patients with ECOG PS=0 had improved survival than PS≥1. There were no statistically significant (p<0.05) differences between AtezoBev and Lenvatinib. Age, sex and social deprivation (SIMD) score had minimal effects on survival although high levels of social deprivation and male sex were over-represented in our population.
Conclusions:
In contrast to other real world analyses, our patients demonstrated improved mOS with Atezo/Bev vs Lenvatinib.
3
However, mPFS was similar for the two regimes. The difference in OS may be explained by differences in patient selection, with the Lenvatinib group disproportionately representing patients with a poorer performance status (PS>0) and higher Childs-Pugh scores (CP>5). Furthermore, patients in the AtezoBev group who progressed were often offered Lenvatinib second-line, possibly improving mOS, whereas Lenvatinib patients who progressed were offered either Sorafenib, a clinical trial or best supportive care. However, we cannot rule out a direct survival benefit from the use of AtezoBev vs Lenvatinib in the first line setting. The choice of first line therapy for HCC remains complex and must account for patient preferences such as convenience and side effect profile in addition to observed trial outcomes and the increasing body of real world evidence. 1. Finn RS et. al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N. Engl. J. Med. 2020 May 14;382(20):1894-1905. 2. Kudo, Masatoshi et. al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018. Volume 391, Issue 10126, 1163 – 1173. 3. Wang, BC. et. al. Lenvatinib Versus Atezolizumab Plus Bevacizumab in the First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Meta-Analysis of Real-World Studies. Targ. Oncol. 2024. 19, 203–212. 4. Casadei-Gardini A et. al. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population. Eur. J. Cancer. 2023; 180:9-20. 5. Rimini M et. al. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis. ESMO Open. 2022 Dec;7(6):100591. 6. Su CW et. al. Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first-line treatment for unresectable hepatocellular carcinoma. Cancer Med. 2023. 12(6):7077-7089. 7. Rimini, M., et al. Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients. J. Cancer. Res. Clin. Oncol. 2023. 149, 7565–7577.