Lenvatinib as Second-Line Treatment after Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma: Clinical Results Show Importance of Hepatic Reserve Function

Atsushi Hiraoka; Takashi Kumada; Toshifumi Tada; Masashi Hirooka; Kazuya Kariyama; Joji Tani; Masanori Atsukawa; Koichi Takaguchi; Ei Itobayashi; Shinya Fukunishi; Kunihiko Tsuji; Toru Ishikawa; Kazuto Tajiri; Hironori Ochi; Satoshi Yasuda; Hidenori Toyoda; Chikara Ogawa; Takashi Nishimura; Takeshi Hatanaka; Satoru Kakizaki; Noritomo Shimada; Kazuhito Kawata; Atsushi Naganuma; Hisashi Kosaka; Tomomitsu Matono; Hidekatsu Kuroda; Yutaka Yata; Hideko Ohama; Fujimasa Tada; Kazuhiro Nouso; Asahiro Morishita; Akemi Tsutsui; Takuya Nagano; Norio Itokawa; Tomomi Okubo; Taeang Arai; Keisuke Yokohama; Michitaka Imai; Yohei Koizumi; Shinichiro Nakamura; Hiroko Iijima; Masaki Kaibori; Yoichi Hiasa; Real-life Practice Experts for HCC (RELPEC) Study Group; and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

doi:10.1159/000531316

Lenvatinib as Second-Line Treatment after Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma: Clinical Results Show Importance of Hepatic Reserve Function

Oncology. 2023;101(10):624-633. doi: 10.1159/000531316. Epub 2023 Jun 12.

Authors

Atsushi Hiraoka¹, Takashi Kumada², Toshifumi Tada³, Masashi Hirooka⁴, Kazuya Kariyama⁵, Joji Tani⁶, Masanori Atsukawa⁷, Koichi Takaguchi⁸, Ei Itobayashi⁹, Shinya Fukunishi¹⁰, Kunihiko Tsuji¹¹, Toru Ishikawa¹², Kazuto Tajiri¹³, Hironori Ochi¹⁴, Satoshi Yasuda¹⁵, Hidenori Toyoda¹⁵, Chikara Ogawa¹⁶, Takashi Nishimura¹⁷, Takeshi Hatanaka¹⁸, Satoru Kakizaki¹⁹, Noritomo Shimada²⁰, Kazuhito Kawata²¹, Atsushi Naganuma²², Hisashi Kosaka²³, Tomomitsu Matono²⁴, Hidekatsu Kuroda²⁵, Yutaka Yata²⁶, Hideko Ohama¹, Fujimasa Tada¹, Kazuhiro Nouso⁵, Asahiro Morishita⁶, Akemi Tsutsui⁸, Takuya Nagano⁸, Norio Itokawa⁷, Tomomi Okubo⁷, Taeang Arai⁷, Keisuke Yokohama¹⁰, Michitaka Imai¹², Yohei Koizumi⁴, Shinichiro Nakamura³, Hiroko Iijima¹⁷, Masaki Kaibori²³, Yoichi Hiasa⁴; Real-life Practice Experts for HCC (RELPEC) Study Group; and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)

Affiliations

¹ Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan.
² Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan.
³ Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan.
⁴ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan.
⁵ Department of Hepatology, Okayama City Hospital, Okayama, Japan.
⁶ Department of Gastroenterology and Hepatology, Kagawa University, Takamatsu, Japan.
⁷ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
⁸ Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
⁹ Department of Gastroenterology, Asahi General Hospital, Asahi, Japan.
¹⁰ Department of Gastroenterology, Osaka Medical and Pharmaceutical University, Osaka, Japan.
¹¹ Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan.
¹² Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan.
¹³ Department of Gastroenterology, Toyama University Hospital, Toyama, Japan.
¹⁴ Hepato-biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.
¹⁵ Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan.
¹⁶ Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan.
¹⁷ Department of Gastroenterology and Hepatology, Hyogo Medical University, Nishinomiya, Japan.
¹⁸ Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Maebashi, Japan.
¹⁹ Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
²⁰ Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan.
²¹ Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan.
²² Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan.
²³ Department of Surgery, Kansai Medical University, Hirakata, Japan.
²⁴ Department of Hepatology, St. Mary's Hospital, Himeji, Japan.
²⁵ Division of Hepatology, Department of Internal Medicine, Iwate Medical University, School of Medicine, Morioka, Japan.
²⁶ Department of Gastroenterology, Hanwa Memorial Hospital, Osaka, Japan.

PMID: 37307798
DOI: 10.1159/000531316

Abstract

Introduction: Lack of an established methodology for post-progression systemic treatment following atezolizumab plus bevacizumab (Atez/Bev) administration is an important clinical issue. The present study aimed to elucidate the potential of lenvatinib as a second-line treatment option after Atez/Bev failure.

Methods: From 2020 to 2022, 101 patients who received lenvatinib as second-line treatment were enrolled (median 72 years, males 77, Child-Pugh A 82, BCLC-A:B:C:D = 1:35:61:4), while 29 treated with another molecular targeting agent (MTA) during the period as second-line treatment were enrolled as controls. The therapeutic efficacy of lenvatinib given as second-line treatment was retrospectively evaluated.

Results: Median progression-free survival/median overall survival for all patients was 4.4/15.7 months and for those with Child-Pugh A was 4.7 months/not-reached. When prognosis was compared with patients who received another MTA, there was no significant difference for PFS (3.5 months, p = 0.557) or OS (13.6 months, p = 0.992), and also no significant differences regarding clinical background factors. mRECIST findings showed that objective response and disease control rates in patients treated with lenvatinib were 23.9% and 70.4%, respectively (CR:PR:SD:PD = 3:14:33:21), while those shown by RECIST, ver. 1.1, were 15.4% and 66.2%, respectively (CR:PR:SD:PD = 1:10:36:24). Adverse events (any grade ≥10%) were appetite loss (26.7%) (grade 1:2:3 = 2:15:10), general fatigue (21.8%) (grade 1:2:3 = 3:13:6), protein in urine (16.8%) (grade 1:2:3 = 0:4:13), and hypertension (13.9%) (grade 1:2:3 = 1:8:5).

Conclusion: Although lenvatinib treatment might not provide a pseudo-combination immunotherapy effect following Atez/Bev failure, lenvatinib when used as second-line treatment after Atez/Bev failure might be expected to be comparable as compared to its use as first-line treatment.

Keywords: Atezolizumab plus bevacizumab; Child-Pugh classification; Hepatocellular carcinoma; Lenvatinib; Modified albumin-bilirubin grade.

MeSH terms

Bevacizumab / adverse effects
Carcinoma, Hepatocellular* / drug therapy
Humans
Liver Neoplasms* / drug therapy
Male
Retrospective Studies

Substances

lenvatinib
Bevacizumab
atezolizumab