Lenvatinib After Atezolizumab–Bevacizumab Failure in Advanced HCC- J Hepatol Feb.26

Atezolizumab plus bevacizumab is the established first-line treatment for unresectable hepatocellular carcinoma (HCC). However, most patients eventually progress, and the optimal second-line therapy after atezo-bev failure remains uncertain, with limited prospective data to guide clinical decisions.

This multicenter, investigator-initiated phase II trial evaluated lenvatinib as a second-line treatment in patients with unresectable HCC who had progressed on first-line atezo-bev. Patients received weight-based oral lenvatinib until disease progression or unacceptable toxicity. The study focused on progression-free survival as the primary endpoint, with overall survival, tumor response, and safety as secondary outcomes.

The study demonstrated that lenvatinib provides meaningful disease control in the post–atezo-bev setting. Progression-free survival exceeded the predefined efficacy threshold, and overall survival outcomes were clinically relevant in a population with limited therapeutic options. Tumor responses were modest but durable in responders, and disease stabilization was achieved in the majority of patients. Importantly, outcomes were driven by response to lenvatinib itself rather than prior response duration to atezo-bev or underlying disease etiology.

The safety profile was consistent with known effects of lenvatinib and was generally manageable with dose modifications and supportive care, despite a substantial rate of higher-grade adverse events.

In summary, this study provides the first prospective evidence supporting lenvatinib as a viable second-line option after atezolizumab–bevacizumab failure in advanced HCC, helping to define a treatment pathway in a rapidly evolving therapeutic landscape.