PD-1抑制剂联合抗血管生成药物治疗晚期NSCLC的疗效及安全性分析

Research on the Efficacy and Safety of PD-1 Inhibitors Combined with Antiangiogenic Drugs in the Treatment of Advanced NSCLC

目的探讨程序性死亡蛋白-1(PD-1)抑制剂联合抗血管生成药物治疗晚期非小细胞肺癌(NSCLC)的疗效及安全性。方法选取我院2019年1月至2021年11月收治的137例晚期NSCLC患者作为研究对象,按治疗方法分为两组。PD-1抑制剂联合抗血管生成药物治疗者81例(联合组),PD-1抑制剂单药治疗者56例(单药组)。统计分析两组客观缓解率(ORR)、疾病控制率(DCR)、无进展生存时间(PFS)、总生存时间(OS)、血管内皮生长因子(VEGF)、肿瘤体积(TV)、预后生存曲线及毒副反应相关数据。结果联合组ORR和DCR显著高于单药组,差异有统计学意义(χ^(2)=4.219,3.583;P=0.040,0.045);联合组PFS和OS均显著长于单药组,差异有统计学意义(Z=7.017,5.778;P<0.001);两组治疗后VEGF和TV水平均明显下降(P<0.001),且治疗1、2个周期后联合组VEGF和TV水平均显著低于单药组,差异有统计学意义(P<0.001);两组Kaplan-Meier预后生存曲线比较差异有统计学意义(χ^(2)_(L)=5.338,P=0.027);两组患者恶心呕吐、头疼、疲劳、腹泻、皮疹、贫血、便秘、呼吸困难及关节痛发生率和Ⅲ级以上毒副反应发生率比较,差异无统计学意义(P>0.05)。结论PD-1抑制剂联合抗血管生成药物可抑制肿瘤微血管增生,缩小TV,提高ORR和DCR,延长PFS和OS,Ⅲ级以上毒副反应发生率低,毒副反应总体安全可控,有助于增加晚期NSCLC患者获益。

Objective To investigate the efficacy and safety of programmed death protein-1(PD-1)inhibitors combined with antiangiogenic agents in the treatment of advanced non-small cell lung cancer(NSCLC).Methods From January 2019 to November 2021,total 137 patients with advanced NSCLC admitted to our hospital were selected as study objects and divided into two groups according to treatment methods.There were 81 patients treated with PD-1 inhibitor combined with antiangiogenic drugs(combination group),and 56 patients treated with PD-1 inhibitor monotherapy(monotherapy group).Objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),vascular endothelial growth factor(VEGF),tumor volume(TV),prognostic survival curve and related data of toxic and side effects were statistically analyzed.Results ORR and DCR in combination group were significantly higher than those in monotherapy group with statistically significant difference(χ^(2)=4.219,3.583;P=0.040,0.045).PFS and OS in combination group were significantly longer than those in monotherapy group with statistically significant difference(Z=7.017,5.778;P<0.001).VEGF and TV in both groups decreased significantly after experiment(P<0.001),and VEGF and TV in combination group were significantly lower than those in monotherapy group after experiment 1 and 2 cycles,with statistical significance(P<0.001).Kaplan-Meier prognosis and survival curves between two groups showed statistically significant difference(χ^(2)_(L)=5.338,P=0.027).The incidence of nausea,vomiting,headache,fatigue,diarrhea,rash,anemia,constipation,dyspnea and arthralgia and the incidence of side effects above gradeⅢwere not statistically significant between two groups(P>0.05).Conclusion PD-1 inhibitors combined with antiangiogenic drugs could inhibit tumor microvascular hyperplasia,reduce TV,increase ORR and DCR,prolong PFS and OS.The incidence of side effects above gradeⅢis low,and the side effects are generally safe and controllable,which helps to increase the benefit of patients with advanced NSCLC.