Real-World Effectiveness of Sorafenib versus Lenvatinib Combined with PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma

被引:6
作者
Chiang, Hsueh-Chien [1 ]
Lee, Yang-Cheng [2 ]
Chang, Ting-Tsung [1 ]
Lin, Yih-Jyh [3 ]
Wu, Hung-Tsung [1 ]
Wang, Chung-Teng [1 ]
Chen, Chiung-Yu [1 ]
Chen, Po-Jun [1 ]
Hsieh, Ming-Tsung [1 ]
Lin, Sheng-Hsiang [4 ,5 ,6 ]
Chen, Shang-Hung [7 ,8 ]
Chuang, Chiao-Hsiung [1 ]
Wu, I-Chin [1 ]
Hong, Tzu-Chun [1 ]
Wu, Juei-Seng [1 ]
Han, Meng-Zhi [9 ]
Chen, Wei-Ting [1 ]
Chiang, Chien-Ming [1 ]
Hung, Kuan-Kai [1 ]
Kuo, Hsin-Yu [1 ,4 ]
机构
[1] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Internal Med, 138 Sheng Li Rd, Tainan 70101, Taiwan
[2] Tainan Municipal Hosp, Dept Internal Med, Tainan 70103, Taiwan
[3] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Surg, Tainan 70101, Taiwan
[4] Natl Cheng Kung Univ, Inst Clin Med, Coll Med, Tainan 70101, Taiwan
[5] Natl Cheng Kung Univ, Coll Med, Dept Publ Hlth, Tainan 70101, Taiwan
[6] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Biostat Consulting Ctr, Tainan 70101, Taiwan
[7] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Oncol, Tainan 70456, Taiwan
[8] Natl Hlth Res Inst, Natl Inst Canc Res, Tainan 70456, Taiwan
[9] China Med Univ, Nan Hosp, Dept Internal Med, Tainan 70965, Taiwan
关键词
immune checkpoint inhibitor; sorafenib; lenvatinib; hepatocellular carcinoma; CHECKPOINT INHIBITORS; VEGF; THERAPY;
D O I
10.3390/cancers15030854
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Simple Summary Immunotherapy using immune checkpoint inhibitors (ICIs) (e.g., programmed cell death protein-1 (PD-1) inhibitors) combined with molecular targeted agents has been evaluated in clinical trials and has shown potential synergic effects and superior efficacy in unresectable hepatocellular carcinoma (uHCC). The optimal regimen for uHCC of combination therapy with a PD-1 inhibitor plus an MTKI remains controversial. A head-to-head comparison is still lacking regarding combination strategies involving the administration of PD-1 inhibitors with different MTKIs in uHCC. This highly original study evaluates the efficacy and safety of PD-1 inhibitors in combination with sorafenib or lenvatinib in a cohort of patients with uHCC. We observed that PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Our data on efficacy and tolerability may enable clinicians to select optimal treatment strategies for HCC therapy. Immune checkpoint inhibitors (ICIs) combined with multitarget tyrosine kinase inhibitors (MTKIs) exert a synergistic effect and are effective in unresectable hepatocellular carcinoma (uHCC). However, precise data regarding the real-world clinical applications of these combination therapies in uHCC are lacking. This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a clinical setting. Among 208 patients with uHCC treated with PD-1 inhibitors, 88 were administered with ICIs in combination with sorafenib or lenvatinib. The treatment response and survival outcomes were evaluated. Predictors of survival were assessed by multivariate analysis. A total of 49 patients were treated with PD-1 inhibitors combined with sorafenib, and 39 patients were treated with PD-1 inhibitors combined with lenvatinib. The lenvatinib group exhibited a stronger objective response rate (ORR) (20.51% vs. 16.33%) and had a higher disease control rate (41.03% vs. 28.57%) than did the sorafenib group. The median overall survival was longer in the lenvatinib group than the sorafenib group (13.1 vs. 7.8 months; hazard ratio = 0.39, p = 0.017). The incidence of treatment-related adverse events was similar. PD-1 inhibitors combined with lenvatinib can be a feasible treatment strategy for HCC patients receiving MTKI-based combination therapy. PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Additional larger-scale and prospective studies should be conducted to verify the study results.
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页数:13
相关论文
共 29 条
[1]   Immune Checkpoint Inhibitors for Unresectable Hepatocellular Carcinoma [J].
Abd El Aziz, Mohamed A. ;
Facciorusso, Antonio ;
Nayfeh, Tarek ;
Saadi, Samer ;
Elnaggar, Mohamed ;
Cotsoglou, Christian ;
Sacco, Rodolfo .
VACCINES, 2020, 8 (04) :1-19
[2]   Anti-PD-1 combined sorafenib versus anti-PD-1 alone in the treatment of advanced hepatocellular cell carcinoma: a propensity score-matching study [J].
Chen, San-Chi ;
Huang, Yi-Hsiang ;
Chen, Ming-Huang ;
Hung, Yi-Ping ;
Lee, Rheun-Chuan ;
Shao, Yu-Yun ;
Chao, Yee .
BMC CANCER, 2022, 22 (01)
[3]   CXCR4 Inhibition in Tumor Microenvironment Facilitates Anti-Programmed Death Receptor-1 Immunotherapy in Sorafenib-Treated Hepatocellular Carcinoma in Mice [J].
Chen, Yunching ;
Ramjiawan, Rakesh R. ;
Reiberger, Thomas ;
Ng, Mei R. ;
Hato, Tai ;
Huang, Yuhui ;
Ochiai, Hiroki ;
Kitahara, Shuji ;
Unan, Elizabeth C. ;
Reddy, Tejaswini P. ;
Fan, Christopher ;
Huang, Peigen ;
Bardeesy, Nabeel ;
Zhu, Andrew X. ;
Jain, Rakesh K. ;
Duda, Dan G. .
HEPATOLOGY, 2015, 61 (05) :1591-1602
[4]   Challenges of combination therapy with immune checkpoint inhibitors for hepatocellular carcinoma [J].
Cheng, Ann-Lii ;
Hsu, Chiun ;
Chan, Stephen L. ;
Choo, Su-Pin ;
Kudo, Masatoshi .
JOURNAL OF HEPATOLOGY, 2020, 72 (02) :307-319
[5]   Treatment of Hepatocellular Carcinoma [J].
Diaz-Gonzalez, Alvaro ;
Reig, Maria ;
Bruix, Jordi .
DIGESTIVE DISEASES, 2016, 34 (05) :597-602
[6]   Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial [J].
El-Khoueiry, Anthony B. ;
Sangro, Bruno ;
Yau, Thomas ;
Crocenzi, Todd S. ;
Kudo, Masatoshi ;
Hsu, Chiun ;
Kim, Tae-You ;
Choo, Su-Pin ;
Trojan, Jorg ;
Welling, Theodore H., III ;
Meyer, Tim ;
Kang, Yoon-Koo ;
Yeo, Winnie ;
Chopra, Akhil ;
Anderson, Jeffrey ;
dela Cruz, Christine ;
Lang, Lixin ;
Neely, Jaclyn ;
Tang, Hao ;
Dastani, Homa B. ;
Melero, Ignacio .
LANCET, 2017, 389 (10088) :2492-2502
[7]   Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma [J].
Finn, Richard S. ;
Qin, Shukui ;
Ikeda, Masafumi ;
Galle, Peter R. ;
Ducreux, Michel ;
Kim, Tae-You ;
Kudo, Masatoshi ;
Breder, Valeriy ;
Merle, Philippe ;
Kaseb, Ahmed O. ;
Li, Daneng ;
Verret, Wendy ;
Xu, Derek-Zhen ;
Hernandez, Sairy ;
Liu, Juan ;
Huang, Chen ;
Mulla, Sohail ;
Wang, Yulei ;
Lim, Ho Yeong ;
Zhu, Andrew X. ;
Cheng, Ann-Lii .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (20) :1894-1905
[8]   Hepatocellular carcinoma [J].
Forner, Alejandro ;
Reig, Maria ;
Bruix, Jordi .
LANCET, 2018, 391 (10127) :1301-1314
[9]   Rationally combining anti-VEGF therapy with checkpoint inhibitors in hepatocellular carcinoma [J].
Hato, Tai ;
Zhu, Andrew X. ;
Duda, Dan G. .
IMMUNOTHERAPY, 2016, 8 (03) :299-313
[10]   Predictive markers of anti-VEGF and emerging role of angiogenesis inhibitors as immunotherapeutics [J].
Hegde, Priti S. ;
Wallin, Jeffrey J. ;
Mancao, Christoph .
SEMINARS IN CANCER BIOLOGY, 2018, 52 :117-124