Cabozantinib for Hepatocellular Carcinoma in Real-World Practice (CLERANCE): A Prospective, Interventional Study.

Background: Cabozantinib is recommended after sorafenib failure in systemic therapy of hepatocellular carcinoma (HCC), based on the results of CELESTIAL. Herein, CLERANCE was designed to evaluate the safety and efficacy of cabozantinib after prior sorafenib failure in real-life setting. Methods: This prospective French multicenter phase-4 trial (NCT03963206) recruited 110 patients with unresectable HCC when a decision of cabozantinib was made in tumor board. The primary endpoint was incidence of grade-3/4 treatment-related adverse events (TRAEs). Secondary endpoints included overall survival, objective response rate, progression-free survival, time to progression, and profiles of cabozantinib tolerance and management. Results: Final analysis focused on the 99 patients who started cabozantinib. Patients were mainly males, Child-Pugh A, and modified-ALBI grade-1/2a/2b. Sorafenib had been discontinued after 4.2 months median administration. Grade-3/4 TRAEs were reported in 61.3% of patients. The objective response rate was 7% with 58% of disease control rate, and median progression-free survival 6.2 months, time to progression 8.2 months, overall survival 11.5 months since the start of cabozantinib and 23.2 months since the start of the first systemic line. Baseline modified-ALBI grade-1+2a and alpha-fetoprotein <400 ng/mL were independent markers of better outcome in multivariate analysis. The median duration of cabozantinib administration was 5.2 months, median daily dose 40 mg, 66% patients needing dose reductions. Conclusions: In CLERANCE, tolerability and efficacy of cabozantinib were similar to those observed in CELESTIAL. We obtained more details in the management of cabozantinib doses, identified surrogate markers of better outcome, and underlined prolonged overall survival for patients able to undergo subsequent lines.