仑伐替尼治疗酪氨酸激酶抑制剂经治不可切除肝细胞癌患者的效果及安全性观察

刘晓民; 孙巍; 魏建莹; 李文东; 丁晓燕; 于明华; 陈京龙

doi:10.3969/j.issn.1001-5256.2022.06.020

仑伐替尼治疗酪氨酸激酶抑制剂经治不可切除肝细胞癌患者的效果及安全性观察

DOI: 10.3969/j.issn.1001-5256.2022.06.020

首都医科大学附属北京地坛医院肿瘤内科，北京 100015

基金项目:

艾滋病和病毒性肝炎等重大传染病防治 (2018ZX10303-502)

伦理学声明：本研究于2019年7月25日经由首都医科大学附属北京地坛医院伦理委员会审批，批号：京地伦科字(2019)第049-001号。

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：刘晓民参与课题设计，数据获取及分析，撰写论文；孙巍、陈京龙参与课题设计，修改论文；魏建莹、李文东、丁晓燕、于明华参与数据获取及数据分析。

详细信息

通信作者:
陈京龙，chejl6412@sina.com

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出版历程
- 收稿日期: 2021-09-28
- 录用日期: 2021-11-29
- 出版日期: 2022-06-20

Efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma previously treated with tyrosine kinase inhibitor

Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China

Research funding:

Prevention and Treatment of Major Infectious Disease such as ADIS and Viral Hepatitis (2018ZX10303-502)

More Information

Corresponding author: CHEN Jinglong, chejl6412@sina.com (ORCID:0000-0003-1640-7115)

摘要

摘要: 目的探索仑伐替尼在酪氨酸激酶抑制剂(TKI)经治不可切除肝细胞癌(HCC)患者中的疗效和安全性。方法收集2019年1月—2020年1月就诊于首都医科大学附属北京地坛医院接受仑伐替尼治疗的76例不可切除HCC患者临床资料，根据治疗方式分为TKI初治组(n=49)和TKI经治组(n=27)。研究观察至入组后1年或调整治疗方案或肿瘤进展或死亡。比较两组无进展生存期(PFS)、客观缓解率(ORR)、疾病控制率(DCR)、不良事件发生率等。计量资料两组间比较采用t检验或Wilcoxon秩和检验。计数资料组间比较用χ²检验或Wilcoxon秩和检验。应用Kaplan-Meier法进行生存分析，组间比较采用log-rank检验。结果 TKI初治组和TKI经治组中位PFS(115 d vs 72 d，P=0.148)、ORR(36.7% vs 18.5%，P=0.098)、DCR(65.3% vs 55.6%，P=0.402)、3级及以上不良事件发生率(24.5% vs 18.5%，P=0.550)比较，差异均无统计学意义。结论 TKI经治不可切除HCC患者可以从仑伐替尼治疗中获益且安全性良好，与TKI初治患者相似。
- 癌, 肝细胞 /
- 仑伐替尼 /
- 治疗结果
Abstract: Objective To investigate the efficacy and safety of lenvatinib in patients with unresectable hepatocellular carcinoma (HCC) previously treated with tyrosine kinase inhibitor (TKI). Methods A retrospective analysis was performed for the clinical data of 76 patients with unresectable HCC who were treated with lenvatinib in Beijing Ditan Hospital, Capital Medical University, from January 2019 to January 2020, and according to the treatment method, they were divided into TKI previously untreated group with 49 patients and TKI treatment-experienced group with 27 patients. The patients were observed till one year after enrollment, adjustment of treatment regimen, tumor progression, or death. The two groups were compared in terms of progression-free survival (PFS) time, objective response rate (ORR), disease control rate (DCR), and incidence rate of adverse events. The t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups, and the chi-square test or the Wilcoxon rank-sum test was used for comparison of categorical data between two groups; the Kaplan-Meier method was used for survival analysis, and the log-rank test was used for comparison between groups. Results There were no significant differences between the TKI previously untreated group and the TKI treatment-experienced group in median PFS time (115 days vs 72 days, P=0.148), ORR (36.7% vs 18.5%, P=0.098), DCR (65.3% vs 55.6%, P=0.402), and incidence rates of grade ≥3 adverse events (24.5% vs 18.5%, P=0.550). Conclusion Patients with unresectable HCC previously treated with TKI can benefit from lenvatinib and have good safety, with similar results to those treated with TKI for the first time.
- Carcinoma, Hepatocellular /
- Lenvatinib /
- Treatment Outcome

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图 1 两组PFS生存曲线比较

Figure 1. Comparison of PFS survival curves between the two groups

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表 1 两组患者基线资料

Table 1. Baseline patient characteristics

指标	TKI初治组(n=49)	TKI经治组(n=27)	统计值	P值
性别[例(%)]			χ²=0.000	0.987
男	40(81.6)	22(81.5)
女	9(18.4)	5(18.5)
年龄(岁)	57.88±10.62	55.67±10.78	t=0.864	0.390
糖尿病[例(%)]			χ²=0.403	0.526
无	41(83.7)	21(77.8)
有	8(16.3)	6(22.2)
HCC家族史[例(%)]			χ²=2.298	0.130
无	43(87.8)	20(74.1)
有	6(12.2)	7(25.9)
HBV感染[例(%)]			χ²=0.362	0.547
有	39(79.6)	23(85.2)
无	10(20.4)	4(14.8)
肝硬化(影像)[例(%)]			χ²=0.034	0.853
无	10(20.4)	6(22.2)
有	39(79.6)	21(77.8)
肝外转移[例(%)]			χ²=1.040	0.308
无	33(67.3)	15(55.6)
有	16(32.7)	12(44.4)
门静脉癌栓[例(%)]			χ²=1.983	0.159
无	19(38.8)	15(55.6)
有	30(61.2)	12(44.4)
AST(U/L)	41.30(28.05~63.05)	41.20(29.50~61.00)	Z=-0.168	0.866
ALT(U/L)	29.10(21.20~53.90)	24.10(22.30~37.10)	Z=-1.020	0.308
TBil(μmol/L)	21.56±12.27	19.85±11.41	t=0.597	0.553
Alb(g/L)	37.27±5.09	36.86±5.12	t=0.329	0.743
PT(s)	12.80(12.00~14.45)	12.20(11.40~14.40)	Z=-1.097	0.273
Child-Pugh分级[例(%)]			χ²=0.009	0.922
A级	35(71.4)	19(70.4)
B级	14(28.6)	8(29.6)
mALBI分级[例(%)]			χ²=0.244	0.621
1+2a	28(57.1)	17(63.0)
2b+3	21(42.9)	10(37.0)
AFP(ng/mL)	240.10(22.79~2 703.93)	236.24(11.62~5 004.65)	Z=-0.051	0.959
AFP [例(%)]			χ²=0.044	0.835
＜400 ng/mL	26(53.1)	15(55.6)
≥400 ng/mL	23(46.9)	12(44.4)
CNLC分期[例(%)]			χ²=-0.052	0.958
1+2	10(20.4)	9(33.3)
3a	23(46.9)	6(22.2)
3b	16(32.7)	12(44.4)
BCLC分期[例(%)]			χ²=1.551	0.213
A+B期	10(20.4)	9(33.3)
C期	39(79.6)	18(66.7)
WBC(×10⁹/L)	4.79(3.57~5.78)	4.64(3.61~5.44)	Z=-0.537	0.591
Hb(g/L)	132.35±20.07	129.65±25.08	t=0.607	0.546
PLT(×10⁹/L)	122.00(88.70~164.00)	108.00(81.00~169.00)	Z=-0.347	0.728
注：CNLC分期，中国肝癌分期。

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