Comparative analysis of lenvatinib use after atezolizumab plus bevacizumab versus lenvatinib as first-line therapy in unresectable hepatocellular carcinoma.

BACKGROUND

Lenvatinib is widely used in hepatocellular carcinoma (HCC), but its efficacy following atezolizumab plus bevacizumab remains unclear. This study compared the therapeutic impact of lenvatinib administered after immunotherapy, following its use as a first-line systemic therapy.

METHODS

This retrospective study analyzed patients with unresectable HCC who received lenvatinib either after atezolizumab plus bevacizumab as second-line therapy or as first-line therapy. Propensity score matching (PSM) was applied to balance baseline characteristics. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were compared.

RESULTS

Following PSM, 63 matched pairs were analyzed. The "After Atezo + Beva" group had larger and more advanced intrahepatic tumors, but PSM balanced the groups' baseline characteristics. Based on mRECIST, the objective response rate and disease control rate were 41.1% and 80.4% in the "After Atezo + Beva" group, and 49.2% and 76.3% in the first-line group. Based on RECIST version 1.1, these were 25.0% and 80.4% vs. 28.8% and 76.3%, respectively. Median PFS was 4.5 vs. 5.2 months (p = 0.233) and median OS was 14.3 vs. 16.0 months (p = 0.769). Grades ≥ 3 AEs occurred more frequently in the "After Atezo + Beva" group (74.9% vs. 50.8%, p = 0.006), with grades ≥ 3 proteinuria in 31.7% vs. 14.3% (p = 0.020) and grades ≥ 3 fatigue in 12.7% vs. 1.6% (p = 0.033).

CONCLUSIONS

Lenvatinib demonstrated comparable efficacy whether used following atezolizumab plus bevacizumab or as first-line therapy in unresectable HCC. These findings support its clinical utility in the post-immune checkpoint inhibitor setting, with attention to AE management.