Author information

¹Medical Oncology, A. Businco Cancer Center, A. R. N. A. S. Brotzu, Cagliari, Italy.

²Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.

³Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.

⁴Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.

⁵Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

⁶Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.

⁷Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.

⁸San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy.

⁹Department of Oncology, ASAN Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

¹⁰Department of Medical Oncology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea.

¹¹Department of Internal Medicine 1, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.

¹²Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Republic of Korea.

¹³Liver Unit-CHTMAD, Vila Real, Portugal.

¹⁴Unit of Medical Oncology 2, University Hospital of Pisa, Pisa, Italy.

¹⁵Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.

¹⁶Oncology Unit 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.

¹⁷Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.

¹⁸Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

¹⁹Section of Gastroenterology and Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties PROMISE, University of Palermo, Palermo, Italy.

²⁰Department of Internal Medicine, Ospedale di Faenza, Faenza, Italy.

²¹Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.

²²Department of Gastroenterology, Okayama City Hospital, Okayama, Japan.

²³Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan.

²⁴Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.

²⁵Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.

²⁶Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.

²⁷Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.

²⁸Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.

²⁹Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.

³⁰Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.

³¹Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.

³²Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.

³³Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan.

³⁴Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.

³⁵Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.

³⁶Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.

³⁷Department of Hepatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

³⁸Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.

³⁹Department of Surgery, Kansai Medical University, Osaka, Japan.

⁴⁰Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.

⁴¹Division of Internal Medicine, Hepatobiliary and Immunoallergic diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

⁴²Medical Oncology, University and University Hospital of Cagliari, Cagliari, Italy.

Abstract

Introduction: The most frequently used first-line treatment in patients with advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab. Upon progression after this treatment, the standard of care in many countries is sorafenib, due to the lack of reimbursement for other drugs. Several randomized trials are currently underway to clarify the best second-line therapy in patients with HCC. This real-world study aimed to compare outcomes reached by lenvatinib and sorafenib second-line therapy in this setting.

Methods: The overall cohort included 891 patients with HCC from 5 countries treated with atezolizumab plus bevacizumab in first-line setting between October 2018 and April 2022. At the data cut-off (May 2022), 41.5% of patients were continuing a first-line treatment, 5.5% were lost at follow-up, and 53.0% of patients had progressive disease after first-line therapy. 51.5% of patients with progressive disease received a second-line treatment, while 48.5% did not receive any subsequent therapy. Between patients receiving second-line treatment, 11.1% of patients underwent transarterial chemoembolization, 21.0% received sorafenib, 35.4% underwent lenvatinib, and 32.5% were treated with other drugs.

Results: Lenvatinib second-line subgroup achieved a median overall survival (mOS) of 18.9 months, significative longer (p = 0.01; hazard ratio [HR]: 2.24) compared to sorafenib subgroup that reached a mOS of 14.3 months. The multivariate analysis highlighted albumin-bilirubin 1 grade (p < 0.01; HR: 5.23) and lenvatinib second-line therapy (p = 0.01; HR: 2.18) as positive prognostic factors for OS. The forest plot highlighted a positive trend in terms of OS in favor of patients treated with lenvatinib second-line regardless of baseline characteristics before first-line therapy.

Conclusion: These results suggest that, in patients with HCC progressed to first-line atezolizumab plus bevacizumab, lenvatinib second-line therapy is associated to an improved survival compared to sorafenib.