Exploration of new positions for cabozantinib for advanced hepatocellular carcinoma in the latest real-world practice

Abstract Background: Cabozantinib was found to be effective as a second-line treatment after sorafenib in patients with advanced hepatocellular carcinoma (HCC) in phase 3 CELESTIAL trial. So far, as immunotherapy has substituted molecular target agents as the primary systemic therapy for advanced HCC, cabozantinib is extensively used in the latest real-world clinical practice in a greatly different position than that shown by the CELESTIAL trial. In the current analysis, we examined the safety and effectiveness of cabozantinib administration in real-life settings for patients with advanced HCC. Methods: We retrospectively obtained data from patients with advanced HCC who received cabozantinib in 3 institutions in Japan between September 14, 2018, and November 30, 2021. Results: During the study period, 23 patients with advanced HCC received cabozantinib. Our cohort included 21.7% of patients with Child-Pugh class B, and 52.2% of patients in fourth-line or later. The median progression-free survival of patients given cabozantinib was 3.7 months (95% confidence interval, 1.5–8.9 months). Regarding patients with Child-Pugh class B or administration in fourth-line or later, the discontinuation rate due to adverse events in patients who initialized at 40 mg or 20 mg was fewer, unlike those who initialized at 60 mg (42.9% vs. 75.0%, p = 0.205). Conclusion: In the era of immunotherapy, cabozantinib is extensively administered to patients with various advanced HCC, indicating that with precise dose reduction initiation, the clinical benefit might be achieved even in patients with poor liver function or at the late line.