Fabian Finkelmeier1,2,3, Bernhard Scheiner4,5, Catherine Leyh6, Jan Best7, Thorben Wilhelm Fründt8, Carolin Czauderna9,10,11, Alica Beutel12, Dominik Bettinger13,14, Johannes Weiß15, Tobias Meischl4,5, Fabian Kütting16, Dirk-Thomas Waldschmidt16, Pompilia Radu17, Michael Schultheiß13, Kai-Henrik Peiffer1, Thomas J Ettrich12, Arndt Weinmann9,10, Henning Wege8, Marino Venerito7, Jean-Francois Dufour17, Christian M Lange6, Matthias Pinter4,5, Oliver Waidmann1,2. 1. Department of Gastroenterology, Hepatology and Endocrinology, University Hospital Frankfurt, Frankfurt, Germany. 2. University Cancer Center Frankfurt, University Hospital Frankfurt, Frankfurt, Germany. 3. Frankfurt Cancer Institute, Goethe University Frankfurt/Main, Frankfurt, Germany. 4. Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. 5. Liver Cancer (HCC) Study Group Vienna, Medical University of Vienna, Vienna, Austria. 6. Department of Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany. 7. Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-Von Guericke University Hospital, Magdeburg, Germany. 8. Department of Medicine, Gastroenterology and Hepatology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 9. Department of Internal Medicine 1, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. 10. Clinical Registry Unit (CRU), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. 11. Department of Medicine I, University Medical Center Schleswig Holstein-Campus Lübeck, Lübeck, Germany. 12. Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany. 13. Department of Medicine II, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 14. Berta Ottenstein Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 15. Division of Hepatology, Department of Medicine II, University Hospital Würzburg, Würzburg, Germany. 16. Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany. 17. Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland.
Abstract
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).
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).
Authors: Richard S Finn; Shukui Qin; Masafumi Ikeda; Peter R Galle; Michel Ducreux; Tae-You Kim; Masatoshi Kudo; Valeriy Breder; Philippe Merle; Ahmed O Kaseb; Daneng Li; Wendy Verret; Derek-Zhen Xu; Sairy Hernandez; Juan Liu; Chen Huang; Sohail Mulla; Yulei Wang; Ho Yeong Lim; Andrew X Zhu; Ann-Lii Cheng Journal: N Engl J Med Date: 2020-05-14 Impact factor: 91.245
Authors: Andrew X Zhu; Richard S Finn; Julien Edeline; Stephane Cattan; Sadahisa Ogasawara; Daniel Palmer; Chris Verslype; Vittorina Zagonel; Laetitia Fartoux; Arndt Vogel; Debashis Sarker; Gontran Verset; Stephen L Chan; Jennifer Knox; Bruno Daniele; Andrea L Webber; Scot W Ebbinghaus; Junshui Ma; Abby B Siegel; Ann-Lii Cheng; Masatoshi Kudo Journal: Lancet Oncol Date: 2018-06-03 Impact factor: 41.316
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: Pablo Maroto; Camillo Porta; Jaume Capdevila; Andrea B Apolo; Santiago Viteri; Cristina Rodriguez-Antona; Lidia Martin; Daniel Castellano Journal: Ther Adv Med Oncol Date: 2022-07-13 Impact factor: 5.485
Authors: Catherine Leyh; Ursula Ehmer; Daniel Roessler; Alexander B Philipp; Florian P Reiter; Petia Jeliazkova; Leonie S Jochheim; Matthias Jeschke; Janina Hammig; Johannes M Ludwig; Jens M Theysohn; Andreas Geier; Christian M Lange Journal: Cancers (Basel) Date: 2022-04-13 Impact factor: 6.575