Lenvatinib versus Sorafenib Second-Line Therapy in Patients with Hepatocellular Carcinoma Progressed to Atezolizumab plus Bevacizumab: A Retrospective Real-World Study
Authors: Persano Mara , Casadei-Gardini Andrea , Tada Toshifumi , Suda Goki , Shimose Shigeo , Kudo Masatoshi , Rossari Federico , Yoo Changhoon , Cheon Jaekyung , Finkelmeier Fabian , Lim Ho Yeong , Presa José , Masi Gianluca , Bergamo Francesca , Amadeo Elisabeth , Vitiello Francesco , Kumada Takashi , Sakamoto Naoya , Iwamoto Hideki , Aoki Tomoko , Chon Hong Jae , Himmelsbach Vera , Iavarone Massimo Alberto , Cabibbo Giuseppe , Montes Margarida , Foschi Francesco Giuseppe , Vivaldi Caterina , Soldà Caterina , Sho Takuya , Niizeki Takashi , Nishida Naoshi , Steup Christoph , Bruccoleri Mariangela , Hirooka Masashi , Kariyama Kazuya , Tani Joji , Atsukawa Masanori , Takaguchi Koichi , Itobayashi Ei , Tsuji Kunihiko , Ishikawa Toru , Tajiri Kazuto , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Ogawa Chikara , Nishimura Takashi , Hatanaka Takeshi , Kakizaki Satoru , Shimada Noritomo , Kawata Kazuhito , Hiraoka Atsushi , Tada Fujimasa , Ohama Hideko , Nouso Kazuhiro , Morishita Asahiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Okubo Tomomi , Imai Michitaka , Kosaka Hisashi , Naganuma Atsushi , Koizumi Yohei , Nakamura Shinichiro , Kaibori Masaki , Iijima Hiroko , Hiasa Yoichi , Mascia Luigi , Foti Silvia , Camera Silvia , Piscaglia Fabio , Scartozzi Mario , Cascinu Stefano , Rimini Margherita 
Published: October 2024

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.