PMID- 36569829 OWN - NLM STAT- MEDLINE DCOM- 20221227 LR - 20230118 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma. PG - 1052937 LID - 10.3389/fimmu.2022.1052937 [doi] LID - 1052937 AB - 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. CI - Copyright (c) 2022 Xie, Chen, Yang, Wang, Zhang, Wang, Wang, Zhang, Xue, Long, Li, Sun, Xun, Liu, Chen, Song, Yang, Lu, Mao, Sang, Lu and Zhao. FAU - Xie, Fucun AU - Xie F AD - 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. AD - 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. AD - 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. AD - 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. FAU - Chen, Bowen AU - Chen B AD - Peking University 302 Clinical Medical School, Beijing, China. FAU - Yang, Xu AU - Yang X AD - 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. FAU - Wang, Huaiyuan AU - Wang H AD - 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. FAU - Zhang, Ge AU - Zhang G AD - 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. FAU - Wang, Yanyu AU - Wang Y AD - 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. FAU - Wang, Yunchao AU - Wang Y AD - 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. FAU - Zhang, Nan AU - Zhang N AD - 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. FAU - Xue, Jingnan AU - Xue J AD - 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. FAU - Long, Junyu AU - Long J AD - 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. FAU - Li, Yiran AU - Li Y AD - 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. FAU - Sun, Huishan AU - Sun H AD - 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. FAU - Xun, Ziyu AU - Xun Z AD - 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. FAU - Liu, Kai AU - Liu K AD - 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. FAU - Chen, Xiangqi AU - Chen X AD - 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. FAU - Song, Yang AU - Song Y AD - 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. AD - 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. FAU - Yang, Xiaobo AU - Yang X AD - 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. FAU - Lu, Zhenhui AU - Lu Z AD - Hepatobiliary and Pancreatic Surgery, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China. FAU - Mao, Yilei AU - Mao Y AD - 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. FAU - Sang, Xinting AU - Sang X AD - 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. FAU - Lu, Yinying AU - Lu Y AD - Peking University 302 Clinical Medical School, Beijing, China. FAU - Zhao, Haitao AU - Zhao H AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221209 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Immune Checkpoint Inhibitors) RN - EE083865G2 (lenvatinib) RN - 0 (Antineoplastic Agents) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/drug therapy MH - Immune Checkpoint Inhibitors/adverse effects MH - Molecular Targeted Therapy MH - Retrospective Studies MH - *Liver Neoplasms/drug therapy MH - *Antineoplastic Agents/adverse effects PMC - PMC9780480 OTO - NOTNLM OT - efficacy OT - hepatocellular carcinoma (HCC) OT - immune checkpoint inhibitor (ICI) OT - lenvatinib OT - molecular targeted agent (MTA) OT - safety COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/27 06:00 MHDA- 2022/12/28 06:00 PMCR- 2022/01/01 CRDT- 2022/12/26 04:23 PHST- 2022/09/24 00:00 [received] PHST- 2022/11/16 00:00 [accepted] PHST- 2022/12/26 04:23 [entrez] PHST- 2022/12/27 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1052937 [doi] PST - epublish SO - Front Immunol. 2022 Dec 9;13:1052937. doi: 10.3389/fimmu.2022.1052937. eCollection 2022.