Real-World Clinical Outcomes of Cabozantinib as a Second-Line Treatment for Advanced Hepatocellular Carcinoma: A Retrospective US Claims Analysis

Abstract

Background: Cabozantinib is indicated for hepatocellular carcinoma (HCC) following first-line (1 L) sorafenib, but the 1 L standard has shifted to immuno-oncology (IO)-based regimens. This study evaluated real-world outcomes among patients with advanced HCC receiving second-line (2 L) cabozantinib following 1 L therapies, including newer regimens.

Patients and methods: US claims data were used to identify adults with advanced HCC initiating 2 L cabozantinib monotherapy (index date). Patients were stratified into three 1 L treatment cohorts: IO monotherapy/IO + IO combination therapy; IO + non-IO combination therapy; or tyrosine kinase inhibitor (TKI) monotherapy. Real-world time to treatment discontinuation (rwTTD), time to next treatment or death (rwTNTD), overall survival (rwOS), and cabozantinib dosing were assessed collectively and by cohort. Adverse events were assessed before/after cabozantinib initiation.

Results: Among 148 patients who received 2 L cabozantinib, 28 were in the IO monotherapy/IO + IO combination therapy cohort, 54 in the IO + non-IO combination therapy cohort, and 66 in the TKI monotherapy cohort. Median rwTTD among all patients was 3.2 months; median rwTNTD was 7.6 months; 12-month rwOS rate was 61.6%. There were no significant differences in these outcomes among the three cohorts. Overall, 44.6% of patients initiated 2 L cabozantinib at 60 mg/day, of whom 39.4% required a dose reduction; 37.8% initiated at 40 mg/day, of whom 16.1% had a dose reduction. Adverse event rates were similar before/after cabozantinib initiation.

Conclusion: Cabozantinib shows consistent effectiveness and safety in the 2 L HCC setting following prior TKIs or IO-based regimens in real-world clinical practice. These findings may inform 2 L treatment decisions.

Keywords: cabozantinib; hepatocellular carcinoma; retrospective studies; treatment outcome.