Efficacy and safety of lenvatinib plus gefitinib in lenvatinib-resistant hepatocellular carcinomas: a prospective, single-arm exploratory trial

Autor: Yaoping Shi, Dan Cui, Lei Xia, Donghua Shi, Guangxin Jin, Siying Wang, Yan Lin, Xiaoyin Tang, Jiachang Chi, Tao Wang, Meng Li, Zicheng Lv, Jiaojiao Zheng, Qi Jia, Wu Yang, Zhen Sun, Fan Yang, Hao Feng, Shengxian Yuan, Weiping Zhou, Wenxin Qin, Rene Bernards, Haojie Jin, Bo Zhai
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Signal Transduction and Targeted Therapy, Vol 9, Iss 1, Pp 1-7 (2024)
Druh dokumentu: article
ISSN: 2059-3635
DOI: 10.1038/s41392-024-02085-8
Popis: Abstract Lenvatinib, a multi-kinase inhibitor, has been approved as first-line treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is limited. We have shown previously that lenvatinib and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combination therapy overcomes lenvatinib resistance in HCC with high level of EGFR expression (EGFRhigh). We present here the results of a single-arm, open-label, exploratory study of lenvatinib plus the EGFR-TKI gefitinib for patients with HCC resistance to lenvatinib (NCT04642547; n = 30). Only patients with EGFRhigh HCC and progressive disease after lenvatinib treatment were recruited in the study. The most frequent adverse events of all grades were fatigue (27 patients; 90%), followed by rash (25 patients; 83.3%), diarrhea (24 patients; 80%), and anorexia (12 patients; 40%). Among 30 patients, 9 (30%) achieved a confirmed partial response and 14 (46.7%) had stable disease according to mRECIST criteria. Based on RECIST1.1, 5 (16.7%) achieved a confirmed partial response and 18 (60%) had stable disease. The estimated median progression free survival (PFS) and overall survival (OS) time were 4.4 months (95% CI: 2.5 to 5.9) and13.7 months (95% CI: 9.0 to NA), respectively. The objective response rate (ORR) of the patients in the present study compares very favorable to that seen for the two approved second line treatments for HCC (cabozantinib ORR of 4%; regorafenib ORR of 11%). Given that this combination was well-tolerated, a further clinical study of this combination is warranted.
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