Efficacy of Lenvatinib as Second-Line Therapy After Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma

<b>Background:</b> Atezolizumab plus bevacizumab (ATZ/BEV) is widely used as first-line therapy for advanced hepatocellular carcinoma (HCC); however, optimal subsequent treatment after ATZ/BEV failure remains unclear. <b>Methods:</b> Between October 2020 and August 2024, 165 patients with unresectable HCC treated with first-line ATZ/BEV were retrospectively analyzed. After excluding patients with insufficient follow-up, outcomes were compared between those who received lenvatinib (LEN) as second-line therapy (<i>n</i> = 49) and those who did not (<i>n</i> = 95). <b>Results:</b> Median overall survival (OS) was significantly longer in the LEN group than in the non-LEN group (20.9 vs. 8.47 months, <i>p</i> < 0.01). LEN administration was independently associated with improved OS (hazard ratio 0.48), and this benefit remained significant after inverse probability weighting adjustment (adjusted hazard ratio 0.50). Among LEN-treated patients, a lower albumin-bilirubin score before ATZ/BEV and a total LEN dose ≥ 400 mg were independent prognostic factors. <b>Conclusions:</b> Lenvatinib as second-line therapy after ATZ/BEV was associated with improved survival in unresectable HCC. Preservation of liver function and the ability to maintain adequate lenvatinib exposure were associated with favorable outcomes, likely reflecting baseline prognosis and treatment feasibility rather than lenvatinib-specific predictive factors.