Francesco Tovoli1, Vincenzo Dadduzio2, Stefania De Lorenzo3, Lorenza Rimassa4,5, Gianluca Masi6, Massimo Iavarone7, Fabio Marra8, Ingrid Garajova9, Maria Pia Brizzi10, Bruno Daniele11, Franco Trevisani12,13, Carlo Messina14, Francesco Di Clemente15, Sara Pini16, Giuseppe Cabibbo17, Alessandro Granito1,13, Mario Domenico Rizzato2,18, Vittorina Zagonel2, Giovanni Brandi3, Tiziana Pressiani5, Piera Federico11, Caterina Vivaldi6, Irene Bergna7, Claudia Campani8, Fabio Piscaglia1,13. 1. Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 2. Medical Oncology Unit 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy. 3. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 4. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. 5. Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. 6. Department of Medical Oncology, Pisa University Hospital, Pisa, Italy. 7. Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy. 8. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. 9. Medical Oncology Unit, University Hospital of Parma, Parma, Italy. 10. Medical Oncology Unit, A.O.U. S. Luigi Gonzaga, Orbassano, Italy. 11. U.O.C. Oncologia, Ospedale del Mare, Napoli, Italy. 12. Semeiotica Medica, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. 13. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 14. Oncology Unit, Santa Chiara Hospital, Trento, Italy. 15. Unità Operativa Semplice Dipartimentale (UOSD) "Oncologia medica" del Valdarno, Montevarchi, Italy. 16. Division of Oncology, AUSL Romagna, Rimini, Italy. 17. Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy. 18. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Abstract
INTRODUCTION: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. METHODS: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. RESULTS: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) > 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) >400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4-14.8) and 5.1 (3.3-6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3-4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS > 0, and AFP >400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. CONCLUSIONS: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials.
INTRODUCTION: Cabozantinib has been approved by the European Medicine Agency (EMA) for hepatocellular carcinoma (HCC) previously treated with sorafenib. Cabozantinib is also being tested in combination with immune checkpoint inhibitors in the frontline setting. Real-life clinical data of cabozantinib for HCC are still lacking. Moreover, the prognostic factors for HCC treated with cabozantinib have not been investigated. METHODS: We evaluated clinical data and outcome of HCC patients who received cabozantinib in the legal context of named patient use in Italy. RESULTS: Ninety-six patients from 15 centres received cabozantinib. All patients had preserved liver function (Child-Pugh A), mostly with an advanced HCC (77.1%) in a third-line setting (75.0%). The prevalence of performance status (PS) > 0, macrovascular invasion (MVI), extrahepatic spread, and alpha-fetoprotein (AFP) >400 ng/mL was 50.0, 30.2, 67.7, and 44.8%, respectively. Median overall survival (OS) and progression-free survival were 12.1 (95% confidence interval 9.4-14.8) and 5.1 (3.3-6.9) months, respectively. Most common treatment-related adverse events (AEs) were fatigue (67.7%), diarrhoea (54.2%), anorexia (45.8%), HFSR (43.8%), weight loss (24.0%), and hypertension (24.0%). Most common treatment-related Grade 3-4 AEs were fatigue (6.3%), HFSR (6.3%), and increased aminotransferases (6.3%). MVI, ECOG-PS > 0, and AFP >400 ng/mL predicted a worse OS. Discontinuation for intolerance and no new extrahepatic lesions at the progression were associated with better outcomes. CONCLUSIONS: In a real-life Western scenario (mostly in a third-line setting), cabozantinib efficacy and safety data were comparable with those reported in its registration trial. Data regarding the prognostic factors might help in patient selection and design of clinical trials.
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