Lenvatinib vs. sorafenib as second-line treatment post atezolizumab plus bevacizumab for hepatocellular carcinoma: The LEVIATHAN study

作者：Pasquale Lombardi, Jung Sun Kim, Giulia Francesca Manfredi, Ciro Celsa, Claudia Angela Maria Fulgenzi, Antonio D’Alessio, Bernardo Stefanini, Nidhi Doshi, Emily Warmington, Thomas U. Marron, Matthias Pinter, Bernhard Scheiner, Beodeul Kang, Ho Yeong Lim, Wei‐Fan Hsu, Brooke Wietharn, Marianna Silletta, Alessandro Parisi, Chun‐Yen Lin, Andrea Dalbeni, Gianluca Masi, Martin Schönlein, Johann von Felden, Fabio Piscaglia, Peter R. Galle, Masatoshi Kudo, Tiziana Pressiani, Lorenza Rimassa, Mario Pirisi, Giuseppe Cabibbo, Hong Jae Chon, David J. Pinato · 发表于：JHEP Reports · 年份：2025 · DOI：10.1016/j.jhepr.2025.101595 · 被引用次数：11 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cholangiocarcinoma and Gallbladder Cancer Studies、Cancer Immunotherapy and Biomarkers

Background Atezolizumab plus bevacizumab (A+B) is a standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). However, optimal sequencing strategies after A+B failure remain undefined. Methods LEVIATHAN is a multicentre, observational study evaluating the efficacy and survival outcomes of patients who progressed on A+B and subsequently received either lenvatinib or sorafenib as second-line therapy. Of 1210 patients treated with first-line A+B between May 2018 and August 2024, 230 eligible patients were included (lenvatinib, n=125 [54.3%]; sorafenib, n=105 [45.7%]). Propensity score matching (PSM) was applied to adjust for baseline imbalances, incorporating independent predictors of overall survival (OS) and response to prior treatment. Results In the overall second-line cohort, lenvatinib was associated with superior median progression-free survival (PFS) (5.5 vs 2.6 months, HR 0.41, p<0.001) and median OS (11.9 vs 7.4 months, HR 0.67, p=0.018) compared to sorafenib. From the start of A+B, the A+B-lenvatinib sequence achieved a median OS of 22.4 months versus 14.3 months with A+B-sorafenib (HR 0.54, p<0.001). These differences persisted in the PSM cohort (median OS: 19.6 vs 13.9 months, HR 0.67, p=0.024). Multivariate analysis identified treatment with lenvatinib as an independent predictor of improved OS alongside AFP ≤400 ng/ml, NLR <3, and absence of portal vein thrombosis. Conclusions The LEVIATHAN study supports lenvatinib as a more effective ...