Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life Cohort.

Background and Aims: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib.
Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients' characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020.
Results: Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (30%) and hepatitis C infection in 21 (24%) patients. Seventy-eight patients (89%) were classified as Barcelona clinic liver cancer (BCLC) stage C. Sixty patients (68%) were Child-Pugh A, whereas 22 (25%) were Child-Pugh B, respectively. Cabozantinib was used as systemic second- and third-line or later treatment in 41 (47%) and 46 (52%) patients, respectively. The following best responses under cabozantinib were documented: partial response in 6 (7%), stable disease in 28 (32%), and progressive disease in 28 (32%) patients, respectively. Fifty-two patients (59%) died during follow-up. The median OS from start of cabozantinib treatment was 7.0 months in the entire cohort and 9.7 months in Child-Pugh A patients, while Child-Pugh B patients had a median OS of 3.4 months, respectively. Thirty-seven (42%) patients fulfilled the CELESTIAL inclusion and exclusion criteria, showing a median OS of 11.1 months. Most common adverse events were fatigue (15.6%) and diarrhea (15.6%).
Conclusion: Cabozantinib treatment was effective, safe, and feasible in patients with advanced HCC in patients with compensated cirrhosis. Patients in the real-life setting had more advanced liver disease - in which 25% of patients were Child-Pugh B. However, OS in patients with Child-Pugh A cirrhosis was similar to that reported in the phase 3 trial (CELESTIAL).
Competing Interests: F.F. received travel support from Abbvie and Ipsen and speaker fees from AbbVie. B.S. received travel support from AbbVie, Gilead, and Ipsen. C.L. reports no conflicts of interest. J.B. served as Consultant for BTGPLC, BMS, MSD, Roche, and Eisai. He served as a Speaker for BTGPLC, Eisai, and Novartis. He received travel support from Ipsen, BTGPLC, and BMS. He is an investigator for MSD, BMS, Lilly. T.W.F. reports no conflicts of interest. C.C. received fees and travel support from Eisai, MSD, Ipsen, and Falk Foundation. A.B. reports no conflicts of interest. D.B. served as a consultant for Bayer Healthcare, Boston Scientific, and Falk Foundation. J.W. served as a consultant/speaker and received travel support from BMS, Eisai, Falk, Gilead, Ipsen, MSD, and Novartis. He is an investigator for MSD. T.M. reports no conflicts of interest. F.K. has received speakers' fees from Bayer, Ipsen, MSD, Eisai, Shire, Sirtex and has received travel grants from Eisai, Janssen, Ipsen, and Novartis. D.T.W. reports no conflicts of interest. M.S. served as a consult for Bayer Healthcare, and Falk Foundation. T.J.E: served as a speaker and/or consultant for AstraZeneca, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Merck Serono, MSD, Roche, and Servier. He received travel support from Ipsen. He received financial support for scientific projects from Servier. A.W. is an Editorial Board Member of Liver Cancer. H.W. served as speaker for Bayer, Eisai, and Ipsen, and as a consultant for Bayer, Eisai, Lilly, BMS, Roche, and Ipsen. He conducts studies for Bayer, Roche, Lilly, MSD, and BMS. M.V. received honoraria from Merck Serono, Bayer Vital, and Sirtex and is a member of the advisory boards of Ipsen, Roche, Bayer, Lilly, Nordic Pharma, BMS, MSD, and Amgen. C.L. served as a speaker and/or consultant for AbbVie, Gilead, MSD, Norgine, Falk, Eisai, Roche, Behring, and travel received support from AbbVie and Gilead. M.P. is an investigator for Bayer, BMS, Lilly, and Roche; he received speaker honoraria from Bayer, BMS, Eisai, Lilly, and MSD; he is a consultant for Bayer, BMS, Ipsen, Eisai, Lilly, MSD, and Roche; he received travel support from Bayer and BMS. J-F.D. served in advisory committees: Abbvie, Bayer, Bristol-Myers Squibb, Falk, Genfit, Genkyotex, Gilead Sciences, HepaRegenix, Intercept, Lilly, Merck, and Novartis. Speaking and teaching: Bayer, Bristol-Myers Squibb, Intercept, Genfit, Gilead Sciences, Novartis, and Roche. O.W. served as a speaker and/or consultant for AstraZeneca, Amgen, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Merck Serono, MSD, Novartis, Roche, Servier, and Shire. He received travel support from Abbvie, Bayer, BMS, Gilead, Ipsen, Medac, and Merck. He received financial support for scientific projects from Else Kröner-Fresenius-Stiftung, IPSEN, Medac, Merck Serono, and Novartis. He is an investigator for Basilea, Incyte, and MSD.
(Copyright © 2021 by S. Karger AG, Basel.)