Clinical efficacy and safety of camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in the treatment of HER-2 negative advanced gastric cancer

Abstract

Abstract:

ObjectiveTo explore the clinical efficacy and safety of the camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in human epidermal growth factor receptor-2 （HER-2） negative advanced gastric cancer.MethodsA total of 66 patients with HER-2 negative advanced gastric cancer and first-line treatment failure in Shandong Cancer Hospital Affiliated to Shandong First Medical University from March 2018 to September 2021 were selected. They were divided into study group （n=22） and control group （n=44） according to the different treatment regimens. The patients in the study group were treated with camrelizumab combined with apatinib and chemotherapy, and the patients in the control group were treated with chemotherapy alone. The short-term efficacy, progression-free survival （PFS）, overall survival （OS） and the occurrence of adverse reactions were compared, and Cox regression analysis was used to analyze the influencing factors of prognosis.ResultsAfter at least 2-4 cycles of treatment, the ORR in the study group and the control group were 9.1% （2/22） and 0 （0/44） respectively, with no statistically significant difference （P=0.108）. DCR in the two groups were 77.3% （17/22） and 45.5% （20/44） respectively, with a statistically significant difference （χ²=6.03,P=0.014）. The study group didn’t reach median OS and the median OS in the control group was 11.7 months, with no statistically significant difference （χ²=1.59,P=0.207）. The study group didn’t reach median PFS and the median PFS in the control group was 3.2 months, with a statistically significant difference （χ²=10.13,P=0.001）. Multivariate Cox regression analysis showed that treatment method was an independent influencing factor for PFS in patients with HER-2 negative advanced gastric cancer （HR=0.33, 95%CI： 0.15-0.75,P=0.008）. In terms of adverse reactions, there was a statistically significant difference in the incidence of elevated alanine aminotransferase between the study group and the control group [31.8% （7/22）vs. 6.8% （3/44）,χ²=5.32,P=0.021]. There were no adverse-related deaths in both groups.ConclusionCompared with chemotherapy alone, camrelizumab combined with apatinib and chemotherapy as a second-line or later therapy in HER-2 negative advanced gastric cancer can prolong PFS and improve DCR, but the incidence of elevated alanine aminotransferase increases significantly.

Key words:Stomach neoplasms,Drug therapy,combination,Camrelizumab,Apatinib

Tang Lin, Xiang Mingyue, Zhang Jianbo, Wang Lili, Gong Heyi, Han Dali. Clinical efficacy and safety of camrelizumab combined with apatinib and chemotherapy as second-line or later therapy in the treatment of HER-2 negative advanced gastric cancer[J]. Journal of International Oncology, 2022, 49(5): 276-281.

Figures/Tables8

一般临床特征	研究组（n=22）	对照组（n=44）	χ²值	P值
性别
男	19（86.4）	31（70.5）	2.02	0.155
女	3（13.6）	13（29.5）	2.02	0.155
年龄(岁)
<65	14（63.6）	27（61.4）	0.03	0.858
≥65	8（36.4）	17（38.6）	0.03	0.858
KPS评分（分）
70~80	8（36.4）	20（45.5）	0.50	0.481
90~100	14（63.6）	24（54.5）	0.50	0.481
吸烟史
无	16（72.7）	33（75.0）	0.04	0.842
有	6（27.3）	11（25.0）	0.04	0.842
饮酒史
无	15（68.2）	35（79.5）	1.03	0.310
有	7（31.8）	9（20.5）	1.03	0.310
病理类型
腺癌	20（90.9）	37（84.1）	0.15	0.704
其他	2（9.1）	7（15.9）	0.15	0.704
肝转移
无	12（54.5）	33（75.0）	2.83	0.093
有	10（45.5）	11（25.0）	2.83	0.093
脑转移
无	22（100）	43（97.7）	-	>0.999
有	0（0）	1（2.3）	-	>0.999
治疗线数
二线	5（22.7）	38（86.4）	26.16	˂0.001
三线及以上	17（77.3）	6（13.6）	26.16	˂0.001

影响因素	HR值	95%CI	P值
性别（男/女）	1.41	0.74~2.71	0.299
年龄（≥65岁/<65岁）	0.71	0.40~1.28	0.251
吸烟（是/否）	0.74	0.38~1.47	0.393
饮酒（是/否）	0.66	0.32~1.37	0.263
KPS评分（≥90分/70~80分）	0.72	0.41~1.28	0.260
病理类型（腺癌/其他类型）	1.76	0.82~3.80	0.146
脑转移（是/否）	1.39	0.19~10.16	0.748
肝转移（是/否）	0.85	0.48~1.53	0.594
治疗线数（三线及以上/二线）	0.57	0.29~1.10	0.091
治疗方法（卡瑞利珠单抗联合阿帕替尼及化疗/单纯化疗）	0.32	0.15~0.67	0.003

影响因素	HR值	95%CI	P值
治疗线数（三线及以上/二线）	0.95	0.45~1.97	0.879
治疗方法（卡瑞利珠单抗联合阿帕替尼及化疗/单纯化疗）	0.33	0.15~0.75	0.008

影响因素	HR值	95%CI	P值
性别（男/女）	0.91	0.44~1.87	0.792
年龄（≥65岁/<65岁）	0.58	0.31~1.10	0.093
吸烟（是/否）	0.79	0.38~1.63	0.527
饮酒（是/否）	0.86	0.41~1.82	0.694
KPS评分（≥90分/70~80分）	0.74	0.40~1.39	0.351
病理类型（腺癌/其他类型）	1.92	0.86~4.27	0.110
脑转移（是/否）	1.00	0.14~7.34	0.997
肝转移（是/否）	0.87	0.46~1.65	0.670
治疗线数（三线及以上/二线）	0.77	0.38~1.60	0.489
治疗方法（卡瑞利珠单抗联合阿帕替尼及化疗/单纯化疗治疗）	0.59	0.26~1.35	0.213

影响因素	HR值	95%CI	P值
年龄	0.54	0.27~1.07	0.075
KPS评分（≥90分/70~80分）	0.73	0.38~1.40	0.337
肝转移（是/否）	0.81	0.35~1.89	0.631
吸烟（是/否）	0.87	0.18~4.24	0.865
饮酒（是/否）	0.78	0.15~4.03	0.767

组别	高血压	心肌炎	甲状腺功能减退	腹泻	食欲减退	乏力	谷草转氨酶升高	谷丙转氨酶升高	血小板减少	白细胞减少	中性粒细胞减少
研究组（n=22）	3（13.6）	3（13.6）	3（13.6）	2（9.1）	6（27.3）	3（13.6）	6（27.3）	7（31.8）	7（31.8）	4（18.2）	3（13.6）
对照组（n=44）	3（6.8）	0（0）	0（0）	3（6.8）	6（13.6）	4（9.1）	5（11.4）	3（6.8）	9（20.5）	1（2.3）	5（11.4）
χ²值	0.21	3.54	3.54	<0.01	1.03	0.02	1.65	5.32	1.03	3.27	<0.01
P值	0.650	0.060	0.060	>0.999	0.310	0.888	0.199	0.021	0.310	0.070	>0.999

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