Eur J Cancer. 2023 Feb;180:9-20.doi: 10.1016/j.ejca.2022.11.017. Epub 2022 Nov 25.
Andrea Casadei-Gardini 1, Margherita Rimini 2, Toshifumi Tada 3, Goki Suda 4, Shigeo Shimose 5, Masatoshi Kudo 6, Jaekyung Cheon 7, Fabian Finkelmeier 8, Ho Yeong Lim 9, Lorenza Rimassa 10, José Presa 11, Gianluca Masi 12, Changhoon Yoo 13, Sara Lonardi 14, Francesco Tovoli 15, Takashi Kumada 16, Naoya Sakamoto 4, Hideki Iwamoto 5, Tomoko Aoki 6, Hong Jae Chon 7, Vera Himmelsbach 8, Tiziana Pressiani 17, Margarida Montes 11, Caterina Vivaldi 12, Caterina Soldà 14, Fabio Piscaglia 15, Atsushi Hiraoka 18, Takuya Sho 4, Takashi Niizeki 5, Naoshi Nishida 6, Christoph Steup 8, Massimo Iavarone 19, Giovanni Di Costanzo 20, Fabio Marra 21, Mario Scartozzi 22, Emiliano Tamburini 23, Giuseppe Cabibbo 24, Francesco Giuseppe Foschi 25, Marianna Silletta 26, Masashi Hirooka 27, Kazuya Kariyama 28, Joji Tani 29, Masanori Atsukawa 30, Koichi Takaguchi 31, Ei Itobayashi 32, Shinya Fukunishi 33, Kunihiko Tsuji 34, Toru Ishikawa 35, Kazuto Tajiri 36, Hironori Ochi 37, Satoshi Yasuda 38, Hidenori Toyoda 38, Chikara Ogawa 39, Takashi Nishimura 40, Takeshi Hatanaka 41, Satoru Kakizaki 42, Noritomo Shimada 43, Kazuhito Kawata 44, Fujimasa Tada 18, Hideko Ohama 18, Kazuhiro Nouso 28, Asahiro Morishita 29, Akemi Tsutsui 31, Takuya Nagano 31, Norio Itokawa 30, Tomomi Okubo 30, Taeang Arai 30, Michitaka Imai 35, Hisashi Kosaka 45, Atsushi Naganuma 46, Yohei Koizumi 28, Shinichiro Nakamura 3, Masaki Kaibori 45, Hiroko Iijima 40, Yoichi Hiasa 27, Valentina Burgio 2, Mara Persano 22, Angelo Della Corte 47, Francesca Ratti 48, Francesco De Cobelli
- 1Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy. Electronic address: email@example.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.
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.