Author information
1Medical Oncology, University and University Hospital of Cagliari, Italy. Electronic address: marapersano@alice.it.
2Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.
3Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
4Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
5Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
6Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
7Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea.
8Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.
9Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, South Korea.
10Liver Unit-CHTMAD, Vila Real, Portugal.
11Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
12Department of Oncology, ASAN Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 05505, South Korea.
13Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
14Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, Bologna, Italy.
15Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
16Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
17Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
18Department of Hepatology, Naples 80131, Italy.
19Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Firenze, Italy.
20Department of Oncology and Palliative Care, Cardinale G Panico, Tricase City Hospital, Tricase, Italy.
21Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy.
22Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy.
23Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy.
24Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
25Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
26Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.
27Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
28Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
29Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
30Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan.
31Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
32Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
33Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
34Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.
35Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
36Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.
37Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan.
38Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
39Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
40Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.
41Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
42Department of Surgery, Kansai Medical University, Osaka, Japan.
43Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
44Department of Medical Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, Italy.
45Medical Oncology, University and University Hospital of Cagliari, Italy.
Abstract
Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab.
Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line.
Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6months) and atezolizumab plus bevacizumab first-line (15.7months; p = 0.12; hazard ratio [HR]= 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who underwent trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8months, p < 0.01; HR=0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0months) and those who underwent TACE (15.9months) had a significative longer OS than patients treated with sorafenib (14.2months; respectively, p = 0.01; HR=0.45, and p < 0.05; HR=0.46).
Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy.