Cabozantinib Following Immunotherapy in Patients with Advanced Hepatocellular Carcinoma

SIMPLE SUMMARY: Management of hepatocellular carcinoma is a rapidly evolving field, with atezolizumab-bevacizumab recently becoming standard of care after showing survival benefit over sorafenib. However, all clinical trials evaluating drugs approved in the second line setting, such as cabozantinib, have been evaluated following progression on sorafenib, not immunotherapy. We sought to determine if cabozantinib is a viable option for patients after progression on immunotherapy. We conducted a retrospective analysis of patients seen at our institution who had disease progression on immunotherapy and subsequently received cabozantinib, reporting patient survival and tolerance of treatment. We found that patients had a median progression free survival of 2.1 months and median overall survival of 7.7 months, and most patients had a manageable side effect profile, suggesting that cabozantinib is a viable treatment option following progression on immunotherapy. ABSTRACT: (1) Background: Cabozantinib, a multikinase inhibitor, is approved by the Food and Drug Administration (FDA) for the treatment of advanced hepatocellular carcinoma (HCC) following progression on sorafenib. Recently, atezolizumab plus bevacizumab has been approved in the first line setting for advanced HCC and has become the new standard of care. Whether cabozantinib improves outcomes following progression on immunotherapy remains unknown. We describe the clinical outcomes following treatment with immunotherapy in patients with advanced HCC who received cabozantinib. (2) Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010–2021 at Mayo Clinic in Minnesota, Arizona, and Florida who received cabozantinib. Median overall survival and progression free survival analyses were performed using the Kaplan–Meier method. Adverse events were determined using Common Terminology Criteria for Adverse Events (CTCAE). (3). Results: We identified 26 patients with advanced HCC who received cabozantinib following progression on immunotherapy. Median progression free survival on cabozantinib therapy was 2.1 months (95% CI: 1.3–3.9) and median overall survival from time of cabozantinib initiation was 7.7 months (95% CI: 5.3–14.9). (4) Conclusion: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown. Our study demonstrates that patients may benefit from treatment with cabozantinib following progression on immunotherapy.