贝伐珠单抗联合靶向治疗对EGFR突变型非小细胞肺癌患者的疗效观察

蒋一玲; 张传领; 陈承; 余洪金; 李薇娜; 方晶; 方勇

doi:10.16766/j.cnki.issn.1674-4152.002047

贝伐珠单抗联合靶向治疗对EGFR突变型非小细胞肺癌患者的疗效观察

doi: 10.16766/j.cnki.issn.1674-4152.002047

1.
浙江萧山医院肿瘤内科，浙江杭州 311201
2.
浙江邵逸夫医院肿瘤内科，浙江杭州 311201

基金项目:

浙江省医药卫生科技计划项目 2019RC256

详细信息

通讯作者:
方勇, E-mail: fangyzju@163.com

中图分类号: R734.2 R730.7
计量
- 文章访问数: 146
- HTML全文浏览量: 112
- PDF下载量: 5
- 被引次数: 0
出版历程
- 收稿日期: 2021-09-25
- 网络出版日期: 2022-02-16

Observation of curative effect of bevacizumab combined with targeted treatment of EGFR mutant lung cancer

1.
Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou, Zhejiang 311201, China

摘要

摘要: 目的探讨贝伐珠单抗联合靶向治疗对表皮生长因子受体(EGFR)突变型非小细胞肺癌(NSCLC)患者近远期预后及免疫状态、不良反应的影响，以期为临床治疗方法的选择提供参考。方法选择2017年9月—2018年9月在浙江萧山医院和浙江省邵逸夫医院接受诊治的EGFR突变型NSCLC患者80例，按照随机数字表法分为对照组和观察组，每组各40例。对照组采用盐酸埃克替尼片治疗，观察组采用贝伐珠单抗联合盐酸埃克替尼片治疗。比较2组患者临床疗效、肿瘤标记物水平、免疫指标水平，并对2组患者生存情况、不良反应情况进行比较。结果观察组疾病控制率(DCR)明显高于对照组(P < 0.05)。治疗后，2组血管内皮生长因子(VEGF)、糖类抗原125(CA125)、细胞角蛋白19片段(CYFRA21-1)水平均明显低于治疗前，且观察组均明显低于对照组(P < 0.05)。治疗后，2组CD3⁺、CD4⁺/CD8⁺水平均明显高于治疗前，且观察组均明显高于对照组(P < 0.05)。观察组患者的生存情况优于对照组(P < 0.05)。观察组不良反应总发生率明显低于对照组(P < 0.05)。结论贝伐珠单抗联合盐酸埃克替尼治疗EGFR突变型NSCLC患者疗效显著，可有效抑制肿瘤细胞增殖，缩小肿瘤体积，改善机体免疫功能，提高患者生存率。
- 贝伐珠单抗 /
- 靶向治疗 /
- 表皮生长因子受体突变型 /
- 非小细胞肺癌 /
- 预后
Abstract: Objective To investigate the effect of bevacizumab combined with targeted therapy on the short- and long-term prognosis, immune status, and side effects of patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), in order to provide reference for the choice of clinical treatment. Methods A total of 80 EGFR-mutant NSCLC patients who were diagnosed and treated in our hospital from September 2017 to September 2018 were selected and divided into control group and observation group according to the random number table method, with 40 cases in each group. The control group was treated with icotinib hydrochloride tablets, and the observation group was treated with bevacizumab combined with icotinib hydrochloride tablets. The clinical efficacy, tumor marker levels, and immune index levels were compared between the two groups of patients, and the survival and toxicity of the two groups were compared. Results The disease control rate (DCR) of the observation group was significantly higher than that of the control group (P < 0.05). After treatment, the levels of vascular endothelial growth factor (VEGF), carbohydrate antigen 125 (CA125), and cytokeratin 19 fragment (CYFRA21-1) in the two groups were significantly lower than those before treatment, and the observation group were significantly lower than those in the control group (P < 0.05). After treatment, the levels of CD3⁺, CD4⁺/CD8⁺ in the two groups were significantly higher than those before treatment, and the observation group were significantly higher than those in the control group (P < 0.05). The survival of patients in the observation group was better than that of the control group (P < 0.05). The total incidence of side effects in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion Bevacizumab combined with icotinib hydrochloride in the treatment of EGFR mutant NSCLC patients has a significant effect, which can effectively inhibit the proliferation of tumor cells, reduce the tumor volume, improve the body's immune function, and improve the survival rate of patients.
- Bevacizumab /
- Targeted therapy /
- Epidermal growth factor receptor mutant /
- Non-small cell lung cancer /
- Prognosis

HTML全文

图 1 2组NSCLC患者生存情况比较

下载: 全尺寸图片幻灯片

表 1 2组NSCLC患者一般资料比较

组别	例数	年龄(x±s，岁)	性别(例)		肿瘤直径(x±s，cm)	病理分期(例)		病理类型(例)
组别	例数	年龄(x±s，岁)	男性	女性	肿瘤直径(x±s，cm)	Ⅲb	Ⅳ	腺癌	鳞癌
对照组	40	61.33±6.23	25	15	3.88±0.85	15	25	27	13
观察组	40	60.18±5.89	23	17	3.72±0.79	14	26	28	12
统计量		0.848^a	0.208^b		0.872^a	0.594^b		0.058^b
P值		0.399	0.648		0.386	0.441		0.809
注：^a为t值，^b为χ²值。

下载: 导出CSV

表 2 2组NSCLC患者疗效比较 [例(%)]

组别	例数	CR	PR	SD	PD	DCR
对照组	40	7(15.56)	13(32.50)	7(15.56)	13(32.50)	27(67.50)
观察组	40	12(30.00)	15(37.50)	9(22.50)	4(10.00)	36(90.00)
注：2组疾病控制率比较，χ²=6.050，P=0.014。

下载: 导出CSV

表 3 2组NSCLC患者肿瘤标记物水平比较(x±s)

组别	例数	CYFRA21-1(μg/L)		CA125(U/mL)		VGEF(ng/L)
组别	例数	治疗前	治疗后	治疗前	治疗后	治疗前	治疗后
对照组	40	40.33±7.23	24.42±5.23^a	87.75±10.71	52.21±9.21^a	538.25±100.39	331.31±85.61^a
观察组	40	39.87±7.51	17.58±4.08^a	88.25±11.13	41.89±8.78^a	531.79±98.26	271.58±79.94^a
t值		0.279	6.522	-0.204	5.129	0.291	3.225
P值		0.781	<0.001	0.838	<0.001	0.772	0.002
注：与治疗前比较，^aP < 0.05。

下载: 导出CSV

表 4 2组NSCLC患者免疫指标水平比较(x±s)

组别	例数	CD3⁺(%)		CD4⁺/CD8⁺
组别	例数	治疗前	治疗后	治疗前	治疗后
对照组	40	55.33±3.23	70.74±3.87^a	1.11±0.29	1.74±0.47^a
观察组	40	54.39±2.98	75.74±3.58^a	1.08±0.38	2.49±0.51^a
t值		1.353	-5.170	0.397	-6.839
P值		0.180	<0.001	0.693	<0.001
注：与治疗前比较，^aP<0.05。

下载: 导出CSV

表 5 2组NSCLC患者不良反应比较 [例(%)]

组别	例数	恶心呕吐	高血压	血小板减少	神经毒性	总发生
对照组	40	4(10.00)	3(7.50)	3(7.50)	2(2.50)	12(30.00)
观察组	40	2(5.00)	1(2.50)	1(2.50)	0(0.00)	4(10.00)
注：2组患者不良反应发生率比较，χ²=5.000，P=0.025。

下载: 导出CSV

参考文献(20)

[1]	王聪慧. 中医药联合吉非替尼治疗中晚期非小细胞肺癌有效性和安全性的Meta分析及试验序贯分析[J]. 中药材, 2019, 42(8): 1938-1946. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYCA201908047.htm
[2]	张双美, 王斌, 陈怡, 等. 长链非编码RNA PVT1对非小细胞肺癌细胞增殖和迁移能力的影响及其机制研究[J]. 中华全科医学, 2019, 17(6): 897-901. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201906004.htm
[3]	杨双宁, 李楠, 王丽萍, 等. 埃克替尼联合化疗治疗EGFR突变型晚期非小细胞肺癌的临床效果[J]. 郑州大学学报(医学版), 2020, 55(1): 53-56. https://www.cnki.com.cn/Article/CJFDTOTAL-HNYK202001013.htm
[4]	潘钦石, 胡丽娟, 林晓梅, 等. 盐酸埃克替尼对肺癌A549细胞PI3K/AKT、HIF-1α信号通路的影响[J]. 中华全科医学, 2016, 14(5): 705-708. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY201605004.htm
[5]	陶虹, 郭丽丽, 吴洪波, 等. 贝伐珠单抗联合化疗对复治晚期非鳞非小细胞肺癌患者的疗效及预后分析[J]. 中国肿瘤临床, 2018, 45(10): 503-507. doi: 10.3969/j.issn.1000-8179.2018.10.402
[6]	王慧芳, 宋利刚. 贝伐珠单抗注射液辅助规范化疗治疗非小细胞肺癌的临床效果[J]. 中国老年学杂志, 2018, 38(21): 5193-5195. doi: 10.3969/j.issn.1005-9202.2018.21.030
[7]	史云舒, 李盼华, 李班班, 等. EGFR基因少见突变型非小细胞肺癌的临床特征及应用EGFR-TKIs治疗效果评价[J]. 中国肺癌杂志, 2019, 22(5): 299-305. https://www.cnki.com.cn/Article/CJFDTOTAL-FAIZ201905007.htm
[8]	郭海荣, 胡继德. TP化疗方案联合贝伐珠单抗治疗晚期NSCLC的效果观察[J]. 实用中西医结合临床, 2020, 20(10): 80-81. https://www.cnki.com.cn/Article/CJFDTOTAL-SZXL202010042.htm
[9]	TANAKA K, NOSAKI K, OTSUBO K, et al. Acquisition of the T790M resistance mutation during afatinib treatment in EGFR tyrosine kinase inhibitor-nave patients with non-small cell lung cancer harboring EGFR mutations[J]. Oncotarget, 2017, 8(40): 68123-68130. doi: 10.18632/oncotarget.19243
[10]	赵秋红, 闫春良, 任冠军. 盐酸埃克替尼对中晚期表皮生长因子受体突变型非小细胞肺癌疗效及免疫指标的影响[J]. 癌症进展, 2020, 18(15): 1589-1592. https://www.cnki.com.cn/Article/CJFDTOTAL-AZJZ202015021.htm
[11]	昂冰, 武乐, 周彩云. 贝伐珠单抗联合顺铂治疗肺癌恶性胸水的临床疗效[J]. 中国肿瘤生物治疗杂志, 2018, 25(11): 1176-1179. doi: 10.3872/j.issn.1007-385X.2018.11.016
[12]	FEI Q, XINGSHENG H, YUTAO L, et al. First-line pemetrexed-platinum doublet chemotherapy with or without bevacizumab in non-squamous non-small cell lung cancer: A real-world propensity score-matched study in China[J]. Chinese J Cancer Res, 2019, 31(5): 749-758. doi: 10.21147/j.issn.1000-9604.2019.05.05
[13]	陈惠, 王汉萍, 张力, 等. 盐酸埃克替尼一线治疗晚期非小细胞肺癌的疗效与安全性[J]. 中华内科杂志, 2017, 56(1): 39-43. doi: 10.3760/cma.j.issn.0578-1426.2017.01.010
[14]	储天晴, 陈姬华, 韩宝惠. 贝伐珠单抗治疗晚期非小细胞肺癌的研究进展[J]. 中华肿瘤杂志, 2018, 40(10): 793-800. doi: 10.3760/cma.j.issn.0253-3766.2018.10.013
[15]	樊慧杰, 袁静, 吴晶晶, 等. VEGFR2多态性对贝伐珠单抗联合化疗一线治疗晚期非小细胞肺癌患者效果及安全性的影响[J]. 中华医学杂志, 2019, 99(2): 99-104. doi: 10.3760/cma.j.issn.0376-2491.2019.02.005
[16]	单艳, 李志刚, 姬卫国, 等. VEGFR2基因V297I位点对贝伐珠单抗联合化疗一线治疗晚期非小细胞肺癌患者临床疗效的影响[J]. 中国肿瘤生物治疗杂志, 2019, 26(1): 67-72. https://www.cnki.com.cn/Article/CJFDTOTAL-ZLSW201901011.htm
[17]	邢若, 王鹏, 刘玉豪. 贝伐珠单抗辅助常规化疗治疗非小细胞肺癌的临床研究[J]. 中国临床药理学杂志, 2019, 35(1): 17-19. https://www.cnki.com.cn/Article/CJFDTOTAL-GLYZ201901005.htm
[18]	蒋友国, 王韬渊, 刘军涛, 等. 贝伐珠单抗联合埃克替尼治疗中晚期非小细胞肺癌的临床研究[J]. 现代药物与临床, 2018, 33(12): 3259-3263. https://www.cnki.com.cn/Article/CJFDTOTAL-GWZW201812040.htm
[19]	MATEU-JIMENEZ M, CURULL V, PIJUAN L, et al. Systemic and tumor Th1 and Th2 inflammatory profile and macrophages in lung cancer: influence of underlying chronic respiratory disease[J]. J Thorac Oncol, 2017, 12(2): 235-248. doi: 10.1016/j.jtho.2016.09.137
[20]	艾斌, 杨轶璠. 贝伐珠单抗在晚期非小细胞肺癌一线治疗中的研究进展[J]. 中国肺癌杂志, 2020, 23(7): 626-630. https://www.cnki.com.cn/Article/CJFDTOTAL-FAIZ202007015.htm