阿帕替尼联合用药二线治疗晚期胃癌的疗效观察

卢常青; 胡婷; 苏方; 汪子书

doi:10.16766/j.cnki.issn.1674-4152.003412

阿帕替尼联合用药二线治疗晚期胃癌的疗效观察

doi: 10.16766/j.cnki.issn.1674-4152.003412

卢常青¹,
胡婷¹,
苏方¹,
汪子书^{1, 2, ,}

1.
蚌埠医科大学第一附属医院肿瘤内科，安徽蚌埠 233004
2.
蚌埠医科大学第一附属医院癌症转化医学安徽省重点实验室

基金项目:

安徽高校自然科学研究重点项目 KJ2019A0329

安徽省临床医学研究转化专项项目 202204295107020038

详细信息

通讯作者:
汪子书，E-mail：wzshahbb@163.com

中图分类号: R735.2 R979.1
计量
- 文章访问数: 131
- HTML全文浏览量: 35
- PDF下载量: 4
- 被引次数: 0
出版历程
- 收稿日期: 2023-04-05
- 网络出版日期: 2024-05-27

Efficacy of apatinib combination in second-line treatment of advanced gastric cancer

LU Changqing¹,
HU Ting¹,
SU Fang¹,
WANG Zishu^{1, 2
, ,}

1.
Department of Medical Oncology, the First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui 233004, China

摘要

摘要: 目的回顾性分析阿帕替尼单药、联合化疗或免疫二线治疗晚期胃癌的疗效及不良反应，探讨影响疗效的因素。方法选择2015年1月—2020年12月蚌埠医科大学第一附属医院收治的经一线化疗失败的145例晚期胃癌患者，按照用药方案分为阿帕替尼单药组(36例)、联合化疗组(94例)、联合免疫组(15例)。采用Kaplan-Meier法比较3种方案二线治疗晚期胃癌的疗效，应用Cox回归模型分析影响疗效的因素。结果在晚期胃癌二线治疗中, 联合化疗与联合免疫组的中位无进展生存期(mPFS)及中位总生存期(mOS)显著高于阿帕替尼单药组(mPFS，8.3个月vs. 3.6个月，P < 0.001；8.4个月vs. 3.6个月，P=0.003；mOS，11.0个月vs. 7.5个月，P < 0.001；14.0个月vs. 7.5个月，P < 0.001)。3种治疗方案的客观缓解率(ORR)依次为5.56%、18.09%、26.67%(P=0.097)，疾病控制率(DCR)依次为19.44%、37.23%、33.33%(P=0.151)，差异均无统计学意义。3种治疗方案中，Ⅲ~Ⅳ级不良反应发生率依次为22.2%(8/36)、19.1%(18/94)、26.7%(4/15)，差异无统计学意义(P=0.863)。晚期胃癌患者ECOG评分、有无腹膜转移及是否联合用药与患者的无进展生存期相关，差异均有统计学意义(P < 0.001)。结论在晚期胃癌二线治疗中，阿帕替尼联合化疗或免疫可以带来更好的疗效，且安全性可靠。
- 胃癌 /
- 阿帕替尼 /
- 联合治疗 /
- 疗效 /
- 安全性
Abstract: Objective To retrospectively analyze the adverse effects and efficacy of apatinib monotherapy, combination chemotherapy, or immune second-line treatment for advanced gastric cancer, and to explore the factors that influence treatment efficacy. Methods The study involved 145 patients with advanced gastric cancer who were admitted to the First Affiliated Hospital of Bengbu Medical University between January 2015 and December 2020.The patients were divided into three groups based on their medication regimen: apatinib single-agent group (n=36), combination chemotherapy group (n=94) and combination immunization group (n=15). The effectiveness of the three second-line treatments for advanced gastric cancer was compared using the Kaplan-Meier method. The study employed a Cox regression model to analyze the factors that impact treatment efficacy. The study employed a Cox regression model to analyze the factors that impact treatment efficacy. Results In the second-line treatment of advanced gastric cancer. The combination chemotherapy and combined immunization group showed significantly higher median progression-free survival (mPFS) and median overall survival (mOS) compared to the apatinib monotherapy group (mPFS, 8.3 months vs. 3.6 months, P < 0.001; 8.4 months vs. 3.6 months, P=0.003; mOS, 11.0 months vs. 7.5 months, P < 0.001; 14.0 months vs. 7.5 months, P < 0.001). The objective response rates (ORRs) for the three treatments were 5.56%, 18.09% and 26.67% (P=0.097), respectively. The disease control rates (DCRs) were 19.44%, 37.23% and 33.33% (P=0.151), respectively. However, the differences were not statistically significant (P > 0.05). The incidence of grade Ⅲ-Ⅳ adverse reactions among the three treatment options was 22.2% (8/36), 19.1%(18/94) and 26.7% (4/15), respectively, and the difference was not statistically significant (P=0.863). The statistical analysis revealed that there was a significant correlation between the ECOG score, peritoneal metastasis, and combination and progression-free survival in patients (P < 0.001). Conclusion In the second-line treatment of advanced gastric cancer, combining apatinib with chemotherapy or immunotherapy can lead to better efficacy while maintaining reliable safety.
- Gastric cancer /
- Apatinib /
- Combination therapy /
- Efficacy /
- Security

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图 1 阿帕替尼及其联合用药二线治疗晚期胃癌的Kaplan-Meier生存分析

注：A为无进展生存；B为总生存分析。

Figure 1. Kaplan-Meier survival analysis of apatinib and its combination therapy in the second-line treatment for advanced gastric cancer

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表 1 3组HER-2阴性晚期胃癌患者临床资料比较

Table 1. Comparison of clinical data among three groups of patients with HER-2 negative advanced gastric cancer

组别	例数	性别(男/女，例)	年龄[M(P₂₅, P₇₅)，岁]	ECOG评分(0~1分/2分，例)	分化程度(低/中，例)	TNM分级(ⅢB~C/Ⅳ，例)	手术史(无/有，例)	胸腹水(无/有，例)	腹膜转移(无/有，例)
单药	36	24/12	57.5(50.0，73.5)	26/10	31/5	5/31	14/22	24/12	28/8
联合化疗	94	69/25	62.0(54.0，71.3)	78/16	84/10	21/73	39/55	72/22	69/25
联合免疫	15	9/6	54.0(48.0，74.0)	12/3	14/1	1/14	8/7	11/4	11/4
统计量		1.425^a	0.995^b	1.882^a	0.605^a	2.805^a	0.943^a	1.329^a	0.274^a
P值		0.508	0.608	0.461	0.727	0.235	0.598	0.572	0.919
注：^a为χ²值，^b为H值。

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表 2 阿帕替尼及其联合用药治疗相关不良反应[例(%)]

Table 2. Adverse reactions associated with Apatinib and its combination therapy [cases (%)]

项目	阿帕替尼(n=36)		阿帕替尼联合化疗(n=94)		阿帕替尼联合免疫(n=15)
项目	Ⅰ~Ⅱ	Ⅲ~Ⅳ	Ⅰ~Ⅱ	Ⅲ~Ⅳ	Ⅰ~Ⅱ	Ⅲ~Ⅳ
骨髓抑制	12(33.3)	3(8.3)	42(44.7)	10(10.6)	3(20.0)	1(6.7)
转氨酶升高	5(13.9)	1(2.8)	22(23.4)	1(1.0)	4(26.7)	1(6.7)
总胆红素升高	3(8.3)	1(2.8)	27(28.7)	5(5.3)	5(33.3)	0
碱性磷酸酶升高	5(13.9)	3(8.3)	15(16.0)	2(2.1)	6(40.0)	0
手足综合征	4(11.1)	3(8.3)	24(25.5)	2(2.1)	3(20.0)	2(13.3)
蛋白尿	11(30.6)	0	26(27.7)	3(3.2)	7(46.7)	1(6.7)
高血压	5(13.9)	1(2.8)	30(31.9)	3(3.2)	2(13.3)	0
腹泻	3(8.3)	0	12(12.8)	0	2(13.3)	0
乏力	3(8.3)	0	16(17.0)	0	3(20.0)	0
恶心呕吐	8(22.2)	0	17(18.0)	0	5(33.3)	0
出血	1(2.8)	0	1(1.0)	0	1(6.7)	0
声嘶	3(8.3)	0	4(4.3)	0	1(6.7)	0
口腔溃疡	0	0	4(4.3)	0	0	0
皮疹	0	0	0	0	1(6.7)	0

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表 3 晚期胃癌患者无进展生存期影响因素的单因素分析

Table 3. Univariate analysis of factors influencing progression-free survival in patients with advanced gastric cancer

项目	例数	中位PFS(月)	χ²值	P值
性别			0.212	0.645
男性	102	7.3
女性	43	7.7
ECOG评分			11.208	0.001
0~1分	116	8.3
2分	29	4.9
胸腹水			6.095	0.014
无	107	7.9
有	38	5.3
分化			0.587	0.444
低分化	129	7.3
中分化	16	-
TNM分期			7.376	0.007
ⅢB~ⅢC期	27	-
Ⅳ期	118	6.9
手术史			0.765	0.382
无	61	7.6
有	84	7.3
腹膜转移			14.509	< 0.001
无	108	8.6
有	37	5.8
联合用药			32.426	< 0.001
否	36	3.6
是	109	8.4
注：“-”为中分化组及TNM分期ⅢB~ⅢC期组中PFS数据尚不成熟，未得出具体值。

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表 4 影响晚期胃癌无进展生存期的Cox回归分析

Table 4. Cox regression analysis of factors influencing progression-free survival in advanced gastric cancer

变量	B	SE	P值	HR值	95% CI
EOCG	0.984	0.255	< 0.001	2.675	1.622~4.411
腹膜转移	0.978	0.250	< 0.001	2.658	1.628~4.341
联合用药	-1.635	0.266	< 0.001	0.195	0.116~0.328
注：各变量赋值方法如下，ECOG，2分=1，0~1分=0；有腹膜转移=1，无腹膜转移=0；联合用药=1，未联合用药=0。

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