Comparative effectiveness of immunotherapy versus lenvatinib in advanced hepatocellular carcinoma: A real-world analysis using target trial emulation
Joseph Ahn, Wee Han Ng, Yee Hui Yeo, Hyun‐Seok Kim, Yun Wang, Hirsh D. Trivedi, Walid S. Ayoub, Alexander Kuo, Nicole E. Rich, Neehar D. Parikh, Ghassan K. Abou‐Alfa, Kevin Sheng‐Kai, Amit Singal, Ju Dong Yang
Abstract
BACKGROUND AND AIMS: Immunotherapy has emerged as an effective treatment for advanced HCC. We aimed to investigate the real-world effectiveness of immunotherapy compared to lenvatinib in HCC. APPROACH AND RESULTS: From the TriNetX database, we used a target trial emulation framework and identified patients with HCC who received first-line treatment with immunotherapy (atezolizumab/bevacizumab or tremelimumab/durvalumab) or lenvatinib between or between August 2018 and December 2023. OS was compared using Kaplan-Meier analysis and Cox proportional hazards regression. After propensity score matching, 1203 patients were included in each group. Immunotherapy was associated with improved OS versus lenvatinib (median survival: 545 vs. 425 d; HR: 0.86, 95% CI: 0.76-0.97). Regarding treatment type, atezolizumab plus bevacizumab showed improved survival compared to lenvatinib (n=1070 in each group; HR: 0.87, 95% CI: 0.77-0.99), while the point estimate favored durvalumab plus tremelimumab versus lenvatinib (HR: 0.81, 95% CI: 0.59-1.12), though this difference was not statistically significant, likely due to small sample size. Regarding etiology, immunotherapy had improved OS compared to lenvatinib in viral hepatitis (n=510 in each group; HR: 0.74, 95% CI: 0.61-0.89) and alcohol-associated liver disease (n=190 in each group; HR: 0.65, 95% CI: 0.49-0.87), but not in metabolic dysfunction-associated steatotic liver diseases (n=156 in each group; HR: 0.96, 95% CI: 0.70-1.31). CONCLUSIONS: In this real-world analysis, immunotherapy was associated with improved OS compared to lenvatinib in advanced HCC, with consistent benefit across most subgroups. These findings support the use of immunotherapy as a first-line treatment for advanced HCC.