Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma

Fucun Xie; Bowen Chen; Xu Yang; Huaiyuan Wang; Ge Zhang; Yanyu Wang; Yunchao Wang; Nan Zhang; Jingnan Xue; Junyu Long; Yiran Li; Huishan Sun; Ziyu Xun; Kai Liu; Xiangqi Chen; Yang Song; Xiaobo Yang; Zhenhui Lu; Yilei Mao; Xinting Sang; Yinying Lu; Haitao Zhao

doi:10.3389/fimmu.2022.1052937

Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma

Front Immunol. 2022 Dec 9:13:1052937. doi: 10.3389/fimmu.2022.1052937. eCollection 2022.

Authors

Fucun Xie^{1

2

3

4}, Bowen Chen⁵, Xu Yang¹, Huaiyuan Wang¹, Ge Zhang¹, Yanyu Wang¹, Yunchao Wang¹, Nan Zhang¹, Jingnan Xue¹, Junyu Long¹, Yiran Li¹, Huishan Sun¹, Ziyu Xun¹, Kai Liu¹, Xiangqi Chen¹, Yang Song^{1

6}, Xiaobo Yang¹, Zhenhui Lu⁷, Yilei Mao¹, Xinting Sang¹, Yinying Lu⁵, Haitao Zhao¹

Affiliations

¹ Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁴ Central Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.
⁵ Peking University 302 Clinical Medical School, Beijing, China.
⁶ Department of Thoracic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁷ Hepatobiliary and Pancreatic Surgery, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China.

Abstract

Background: Lenvatinib is a standard first-line systemic therapy in advanced hepatocellular carcinoma (aHCC) and is widely used in all lines. However, the efficacy and safety of immune checkpoint inhibitors (ICIs) plus molecular targeted agents (MTAs) after the progression of lenvatinib treatment are unclear.

Objective: The aim of this study was to evaluate the anticancer effects of ICI plus MTA in patients with aHCC who progressed after lenvatinib.

Methods: We retrospectively included aHCC patients treated with ICI plus MTA after the progression of lenvatinib from two medical centers. Participants who continued lenvatinib treatment were classified into the "ICI+Lenva" group, while the "ICI+Others" group included patients receiving other MTAs. The efficacy endpoints were progression-free survival (PFS), post-progression survival (PPS), overall survival (OS), and tumor response following RECIST v1.1. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0.

Results: In this study, 85 eligible aHCC patients were enrolled, including 58 in the ICI+Lenva group and 27 in the ICI+Others group. At a median follow-up time of 22.8 months, the median PPS and PFS were 14.0 (95% CI: 9.0-18.2) and 4.5 months (95% CI: 3.5-8.3), respectively. The objective response and disease control rates were 10.6% and 52.9%, respectively. No significant differences were observed in any of the efficacy endpoints between the two groups. Prolonged PPS was associated with Child-Pugh grade A, AFP < 400 IU/ml, and concomitant locoregional treatment. All patients experienced adverse events (AEs), but no fatal AEs were observed.

Conclusion: ICI plus MTA in aHCC patients after the progression of lenvatinib presented high antitumor activity and safety. Patients could continue lenvatinib treatment and receive ICIs as well as locoregional treatment to achieve better OS.

Keywords: efficacy; hepatocellular carcinoma (HCC); immune checkpoint inhibitor (ICI); lenvatinib; molecular targeted agent (MTA); safety.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / adverse effects
Carcinoma, Hepatocellular* / drug therapy
Humans
Immune Checkpoint Inhibitors / adverse effects
Liver Neoplasms* / drug therapy
Molecular Targeted Therapy
Retrospective Studies

Substances

Immune Checkpoint Inhibitors
lenvatinib
Antineoplastic Agents