Comparative efficacy of cabozantinib or lenvatinib following atezolizumab plus bevacizumzb in patients with advanced hepatocellular cancer.

4123 Background: Atezolizumab plus bevacizumab is the most commonly utilized first-line therapy for advanced HCC. However, the optimal choice for second-line treatment remains uncertain, particularly between different tyrosine kinase inhibitors including lenvatinib and cabozantinib. This study aims to compare survival outcomes of patients with metastatic HCC who received either lenvatinib or cabozantinib as second-line therapy following frontline treatment with atezolizumab plus bevacizumab. Methods: This retrospective cohort study utilized the TriNetX database, a large-scale platform providing access to deidentified electronic medical records from over 130 million patients across 94 healthcare organizations in the United States. The study included patients diagnosed with metastatic HCC (ICD-10 codes: C22, C22.8) who were aged 18 years or older, diagnosed between January 2019 and October 2024, and had received first-line chemotherapy with atezolizumab and bevacizumab. The cohort was divided into two groups: one receiving lenvatinib and the other cabozantinib as second-line therapy. The primary outcome was overall survival (OS), compared between the two treatment groups using 1:1 propensity score matching (PSM) to balance baseline demographics and comorbidities. Kaplan-Meier survival analysis, log-rank tests, and hazard ratios (HR) were employed to assess differences in OS. Results: Between January 2019 and October 2024, a total of 552 patients met the study criteria, including 397 patients who received Lenvatinib and 155 patients who received cabozantinib as second-line therapy. Median age was similar in two groups (65.2 vs 65.9 yrs). There were no differences between the two groups with respect to gender, albumin or bilirubin levels. Lenvatinib group had lower proportions of white patients (44.1% vs 55.3%). After PSM (matched on age, race, gender, albumin and bilirubin), the final analysis included 151 patients in each treatment group. Kaplan-Meier survival curves demonstrated no statistically significant difference in OS between the two groups (median OS: 16.6 vs 10.9 months; HR: 0.809; 95%CI: 0.576-1.136; p=0.597). Conclusions: This retrospective cohort study found no significant difference in OS in pts with metastatic HCC treated with lenvatinib or cabozantinib as second-line therapy following atezolizumab plus bevacizumab. These findings suggest that both agents may offer comparable survival benefits, highlighting the need for further prospective studies to refine second-line treatment strategies for advanced HCC.