特瑞普利单抗联合贝伐珠单抗二线以上治疗MSI-H型转移性结直肠癌的疗效及安全性

摘要/Abstract

摘要：

目的观察特瑞普利单抗联合贝伐珠单抗二线以上治疗微卫星高度不稳定(MSI-H)型转移性结直肠癌(mCRC)患者的疗效及安全性。方法选取2019年2月至2019年9月广东医科大学附属第三医院收治的56例MSI-H型mCRC患者,采用随机数字表法分为对照组和试验组,各28例。对照组采用贝伐珠单抗治疗,试验组使用特瑞普利单抗联合贝伐珠单抗治疗。比较两组客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期、总生存期以及不良反应发生率。结果试验组ORR为60.71%(17/28),DCR为75.00%(21/28),高于对照组的28.57%(8/28)、46.63%(13/28),差异有统计学意义(χ²=5.85,P=0.016;χ²=4.79,P=0.029)。对照组和试验组患者中位无进展生存期分别为3.5个月和5.8个月,差异有统计学意义(χ²=9.83,P=0.003);对照组和试验组患者中位总生存期分别为12.1个月和16.2个月,差异有统计学意义(χ²=6.13,P=0.007)。对照组和试验组血液学反应(17.86% vs.14.29%,χ²=0.13,P=0.716)、心血管损伤(10.71% vs.14.29%,χ²=0.16,P=0.686)、肝肾功能损伤(25.00% vs.21.43%,χ²=0.10,P=0.752)、胃肠道反应(28.57% vs.35.71%,χ²=0.33,P=0.567)、皮肤黏膜损伤(7.14% vs.10.71%,χ²=0.35,P=0.553)、神经系统疾病(3.57% vs.14.29%,χ²=2.25,P=0.134)、内分泌反应(3.57% vs.10.71%,χ²=1.29,P=0.256)、脱发(14.29% vs.17.86%,χ²=0.13,P=0.716)、疲劳(25.00% vs.28.57%,χ²=0.27,P=0.605)不良反应发生率比较,差异均无统计学意义。结论特瑞普利单抗联合贝伐珠单抗可提高MSI-H型mCRC患者近期和中远期疗效,安全可靠。

关键词:结直肠肿瘤,治疗效果,特瑞普利单抗,贝伐珠单抗,药物相关性副作用和不良反应

Abstract:

ObjectiveTo observe the efficacy and safety of teriprizumab combined with bevacizumab in above the second line treatment of high-level microsatellite instability (MSI-H) type metastatic colorectal cancer (mCRC) patients.MethodsFrom February 2019 to September 2019, 56 patients with MSI-H mCRC admitted to the Third Affiliated Hospital of Guangdong Medical University were selected and divided into control group and test group by random number table method, with 28 cases in each group. The control group was treated with bevacizumab, and the test group was treated with teriprizumab combined with bevacizumab. The objective response rate (ORR), disease control rate (DCR), progression-free survival, overall survival and incidence of adverse reactions were compared between the two groups.ResultsThe ORR and DCR of the test group were 60.71% (17/28) and 75.00% (21/28) respectively, higher than 28.57% (8/28) and 46.63% (13/28) of the control group, with statistically significant differences (χ²=5.85,P=0.016;χ²=4.79,P=0.029). The median progression-free survival of patients in the control group and the test group were 3.5 months and 5.8 months respectively, with a statistically significant difference (χ²=9.83,P=0.003). The median overall survival of patients in the control group and the test group were 12.1 months and 16.2 months respectively, with a statistically significant difference (χ²=6.13,P=0.007). There were no significant diffe-rences in the incidences of hematological reaction (17.86%vs.14.29%,χ²=0.13,P=0.716), cardiovascular injury (10.71%vs.14.29%,χ²=0.16,P=0.686), liver and kidney function injury (25.00%vs.21.43%,χ²=0.10,P=0.752), gastrointestinal reaction (28.57%vs.35.71%,χ²=0.33,P=0.567), skin and mucosal injury (7.14%vs.10.71%,χ²=0.35,P=0.553), nervous system disease (3.57%vs.14.29%,χ²=2.25, P=0.134), endocrine reaction (3.57%vs.10.71%,χ²=1.29,P=0.256), alopecia (14.29%vs.17.86%,χ²=0.13,P=0.716) and fatigue (25.00%vs.28.57%,χ²=0.27,P=0.605) between the control group and the test group.ConclusionThe combination of teriprizumab and bevacizumab can improve the short-term and medium-long-term efficacy of patients with MSI-H mCRC, which is safe and reliable.

Key words:Colorectal neoplasms,Treatment outcome,Teriprizumab,Bevacizumab,Drug-related side effects and adverse reactions

林榕生, 吴楚海, 郭颖梅, 王涛, 陈荣斌, 刘少琴, 甘兵. 特瑞普利单抗联合贝伐珠单抗二线以上治疗MSI-H型转移性结直肠癌的疗效及安全性[J]. 国际肿瘤学杂志, 2022, 49(2): 100-105.

Lin Rongsheng, Wu Chuhai, Guo Yingmei, Wang Tao, Chen Rongbin, Liu Shaoqin, Gan Bing. Efficacy and safety of teriprizumab combined with bevacizumab in the treatment of metastatic MSI-H colorectal cancer above the second line[J]. Journal of International Oncology, 2022, 49(2): 100-105.

图/表4

表1

两组MSI-H型mCRC患者一般资料比较[ x ?±s/例(%)]"

项目	对照组(n=28)	试验组(n=28)	t/χ²值	P值
年龄(岁)	58.46±4.32	57.75±4.59	0.60	0.554
体重指数(kg/m²)	22.15±1.58	22.34±1.83	0.40	0.679
性别
女	12(42.86)	13(46.43)	0.07	0.788
男	16(57.14)	15(53.57)
肿瘤部位
结肠	13(46.43)	15(53.57)	0.29	0.593
直肠	15(53.57)	13(46.43)
转移部位
肝/肺	21(75.00)	19(67.86)	0.35	0.554
其他	7(25.00)	9(32.14)
转移病灶数目
1个	18(64.29)	20(71.43)	0.33	0.567
≥2个	10(35.71)	8(28.57)
病理分化程度
高中分化	16(57.14)	15(53.57)	0.07	0.788
低分化	12(42.86)	13(46.43)
治疗线数
二线	20(71.43)	21(75.00)	0.09	0.763
三线	8(28.57)	7(25.00)

表1

图1

图2

表2

两组MSI-H型mCRC患者不良反应比较"

不良反应	对照组(n=28)			试验组(n=28)			χ²值	P值
不良反应	1~2级(例)	3~4级(例)	发生率(%)	1~2级(例)	3~4级(例)	发生率(%)	χ²值	P值
血液学反应	4	1	17.86	3	1	14.29	0.13	0.716
心血管损伤	3	0	10.71	3	1	14.29	0.16	0.686
肝肾功能损伤	5	2	25.00	5	1	21.43	0.10	0.752
胃肠道反应	6	2	28.57	7	3	35.71	0.33	0.567
皮肤黏膜损伤	2	0	7.14	3	0	10.71	0.35	0.553
神经系统疾病	1	0	3.57	3	1	14.29	2.25	0.134
内分泌反应	1	0	3.57	2	1	10.71	1.29	0.256
脱发	3	1	14.29	4	1	17.86	0.13	0.716
疲劳	6	1	25.00	6	2	28.57	0.27	0.605

表2

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