卡瑞利珠单抗联合安罗替尼治疗晚期胃癌的疗效及对近期预后的影响

目的:探讨卡瑞利珠单抗联合安罗替尼治疗晚期胃癌的疗效及对近期预后的影响,为临床治疗提供参考。方法:选取2019年1月至2020年1月该院收治的ⅢB—Ⅳ期二线治疗失败的胃癌患者100例,采用随机数字表法分为对照组和观察组。对照组患者(50例)给予安罗替尼10 mg,第1—14日,口服,治疗4个周期(3周为1个治疗周期);观察组患者(50例)在对照组的基础上加用卡瑞利珠单抗200 mg,第1日,静脉注射,治疗4个周期(3周为1个治疗周期),出院后保持随访。比较两组患者的疗效、安全性、生存时间和血清血管内皮生长因子(VEGF)水平,外周血CD4⁺T细胞和CD8⁺T细胞上程序性细胞死亡受体1(PD-1)表达的差异;并观察不同微卫星不稳定性(MSI)状态高MSI(MSI-H)、低MSI(MSI-L)和无MSI(MSS)]患者上述指标情况。结果:88例患者进入结果分析。(1)观察组患者的疾病控制率79.07%(34/43)]明显高于对照组57.78%(26/45)],差异有统计学意义(P<0.05)。观察组MSI-H+MSI-L患者的客观有效率50.00%(6/12)]明显高于MSS患者6.45%(2/31)],差异有统计学意义(P<0.05)。(2)观察组患者治疗后血清VEGF水平、外周血CD4⁺T细胞PD-1表达和CD8⁺T细胞PD-1表达明显低于对照组,差异均有统计学意义(P<0.05)。观察组MSI-H+MSI-L患者治疗后外周血CD4⁺T细胞PD-1表达、CD8⁺T细胞PD-1表达明显低于MSS患者,差异均有统计学意义(P<0.05),血清VEGF水平与MSS患者的差异无统计学意义(P>0.05)。(3)两组患者Ⅲ度及以上不良反应发生率的差异无统计学意义(P>0.05)。(4)中位随访时间16(12~20)个月,失访9例。观察组患者的中位无进展生存期、中位总生存期明显长于对照组,且观察组MSI-H+MSI-L患者中位无进展生存期、中位总生存期明显长于MSS患者,差异均有统计学意义(P<0.05)。结论:卡瑞利珠单抗联合安罗替尼三线治疗晚期胃癌,可提高患者的疾病控制率,延长生存时间,安全性可控,对于MSI-H+MSI-L患者的效果更好。

Efficacy of Carrelizumab Combined with Amlotinib in the Treatment of Advanced Gastric Cancer and Its Effect on Short-Term Prognosis

OBJECTIVE:To probe into the efficacy of carrelizumab combined with amlotinib in the treatment of advanced gastric cancer and its effect on short-term prognosis,so as to provide reference for clinical treatment.METHODS:From Jan.2019 to Jan.2020,100 patients with stageⅢB toⅣgastric cancer who failed the second-line treatment in this hospital were extracted to be divided into the control group and the observation group via the random number table.Patients in the control group(n=50)received anlotinib 10 mg orally from the 1st to 14th day of treatment for 4 cycles(3 weeks as a treatment cycle).The observation group(n=50)was additionally given 200 mg carrelizumab intravenously on the 1st day of treatment for 4 cycles(3 weeks as a treatment cycle),and follow-up was maintained after discharge.The efficacy,safety,survival time,serum vascular endothelio genic factor(VEGF)level and programmed cell death receptor 1(PD-1)expression on CD4⁺T cells and CD8⁺T cells in peripheral blood were compared between two groups.The above indicators of patients with different microsatellite instability(MSI)status were observed(MSI-H for high MSI,MSI-L for low MSI,and MSS for no MSI).RESULTS:Eighty-eight patients were enrolled for the results analysis.(1)The disease control rate in the observation group79.07%(34/43)]was significantly higher than that in the control group57.78%(26/45)],the difference was statistically significant(P<0.05).In the observation group,the objective effective rate of MSI-H+MSI-L patients50.00%(6/12)]was significantly higher than that of MSS patients6.45%(2/31)],the difference was statistically significant(P<0.05).(2)After treatment,the levels of serum VEGF,peripheral blood CD4⁺T cells PD-1 and CD8⁺T cells PD-1 in the observation group were significantly lower than those in the control group,with statistically significant difference(P<0.05).After treatment,CD4⁺T cells PD-1 and CD8⁺T cells PD-1 in peripheral blood of MSI-H+MSI-L patients were significantly lower than those of MSS patients in the observation group,with statistically significant differences(P<0.05),while there was no statistically significant difference in serum VEGF level between MSI-H+MSI-L patients and MSS patients(P>0.05).(3)There was no significant difference in the incidence of gradeⅢor above adverse drug reactions between two groups(P>0.05).(4)The median follow-up was 16(from 12 to 20)months,and 9 cases were lost to follow-up.The median progression-free survival time and median overall survival time in the observation group were longer than those in the control group,and the median progression-free survival time and median overall survival time in MSI-H+MSI-L patients were longer than those in MSS patients in the observation group,with statistically significant difference(P<0.05).CONCLUSIONS:Carrelizumab combined with amlotinib in the treatment of advanced gastric cancer can improve the rates of DCR and prolong the survival time with higher safety,especially in MSI-H+MSI-L patients.