Author information

• ¹Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy. Electronic address: casadeigardini@gmail.com.
• ²Department of Oncology, IRCCS San Raffaele Scientific Institute Hospital, Vita-Salute San Raffaele University, 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 830-0011, Japan.
• ⁶Department of Gastroenterology and Hepatology, Kindai University, Faculty of Medicine, Japan.
• ⁷Department of Medical Oncology, CHA Bundang Medical Center, CHA University, Seongnam 13496, 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.
• ¹⁰Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy; Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
• ¹¹Liver Unit-CHTMAD, Vila Real, Portugal.
• ¹²Unit 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.
• ¹³Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
• ¹⁴Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
• ¹⁵Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15 Bologna- Italy.
• ¹⁶Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
• ¹⁷Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano (Milan), Italy.
• ¹⁸Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
• ¹⁹Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.
• ²⁰Department of Hepatology, Naples, 80131, Italy.
• ²¹Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Firenze, Italy.
• ²²Azienda Ospedaliera Universitaria (AOU) Cagliari, University Hospital and University of Cagliari, Cagliari, Italy.
• ²³Department of Oncology and Palliative Care, Cardinale G Panico, Tricase City Hospital, Tricase, Italy.
• ²⁴Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, 90127 Palermo, Italy.
• ²⁵Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy.
• ²⁶Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy.
• ²⁷Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
• ²⁸Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.
• ²⁹Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.
• ³⁰Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
• ³¹Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
• ³²Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
• ³³Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan.
• ³⁴Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
• ³⁵Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
• ³⁶Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
• ³⁷Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.
• ³⁸Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
• ³⁹Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.
• ⁴⁰Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan.
• ⁴¹Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
• ⁴²Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
• ⁴³Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.
• ⁴⁴Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
• ⁴⁵Department of Surgery, Kansai Medical University, Osaka, Japan.
• ⁴⁶Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
• ⁴⁷Department of Radiology, IRCCS San Raffaele Hospital, Milan, Italy; Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Universita Vita-Salute San Raffaele, Milan, Italy.
• ⁴⁸Hepatobiliary Surgery Division, IRCCS San Raffaele Hospital, Milan, Italy.
• ⁴⁹Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.
• ⁵⁰Department of Medical and Surgical Sciences - DIMEC, Alma Mater Studiorum - Univeristy of Bologna, Bologna, Italy.

Abstract

Background and aims: Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomised controlled trial. We conducted a retrospective multi-centre study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario.

Methods: Clinical features of lenvatinib and atezolizumab plus bevacizumab patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival (OS) was the primary end-point.

Results: The analysis included 1341 patients who received lenvatinib, and 864 patients who received atezolizumab plus bevacizumab. After IPTW adjustment, atezolizumab plus bevacizumab did not show a survival advantage over lenvatinib HR 0.97 (p = 0.739). OS was prolonged by atezolizumab plus bevacizumab over lenvatinib in viral patients (HR: 0.76; p = 0.024). Conversely, OS was prolonged by lenvatinib in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (HR: 1.88; p = 0.014). In the IPTW-adjusted population, atezolizumab plus bevacizumab provided better safety profile for most of the recorded adverse events.

Conclusion: Our study did not identify any meaningful difference in OS between atezolizumab plus bevacizumab and lenvatinib. Although some hints are provided suggesting that patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease might benefit more from lenvatinib therapy and patients with viral aetiology more from atezolizumab plus bevacizumab.