摘要
目的评价程序性死亡受体1(PD-1)抑制剂联合化疗一线治疗人表皮生长因子受体2(HER2)阴性晚期胃或胃食管交界部癌(G/GEJC)的有效性及安全性。方法检索中国知网、万方、Pubmed、Cochrane、Embase、Web of Science、Clinical Trials.gov等数据库和中国抗癌协会、韩国临床肿瘤学会、日本临床肿瘤学会等会议摘要中有关PD-1抑制剂联合化疗一线治疗HER2阴性晚期G/GEJC患者的临床随机对照试验(RCT),筛选文献,提取资料,采用R 4.3.1进行Meta分析。结果纳入5篇RCT共5297例HER2阴性晚期G/GEJC的成年患者。PD-1抑制剂联合化疗一线治疗可延长患者的总生存期(OS)(HR=0.79,95%CI:0.74~0.85,P<0.001)及无进展生存期(PFS)(HR=0.74,95%CI:0.69~0.80,P<0.001),并提高客观有效率(ORR)(RR=1.23,95%CI:1.15~1.31,P<0.001)。亚组分析结果显示:在综合阳性分数(CPS)≥1、CPS≥5、CPS≥10的患者中,PD-1抑制剂联合化疗一线治疗方案的OS、PFS、ORR均获益,且程序性死亡配体1表达程度越高,疗效获益均更佳。此外,微卫星高度不稳定性(MSI-H)的患者PD-1抑制剂联合化疗一线治疗方案延长OS更为显著(HR=0.35,95%CI:0.21~0.59,P<0.001)。与化疗组相比,PD-1抑制剂联合化疗一线治疗方案未增加治疗相关不良反应的发生率(P>0.05)。结论PD-1抑制剂联合化疗一线治疗HER2阴性晚期G/GEJC的疗效优于化疗,且高CPS或MSI-H患者获益更大,具有良好的安全性。
Objective To evaluate the efficacy and safety of programmed death receptor 1(PD-1)inhibitors combined with chemotherapy as first-line treatment for patients with human epidermal growth factor receptor2(HER2)-negative advanced gastric or gastroesophageal junction cancer(G/GEJC).Methods Databases such as China National Knowledge Infrastructure,Wanfang,Pubmed,Cochrane,Embase,Web of Science,Clinical Trials.gov,and the abstracts of studies reported in important conferences such as Chinese Society of Clinical Oncology,Korean Society of Medical Oncology,Japanese Society of Clinical Oncology were searched for clinical randomized controlled trials(RCTs)on the first-line treatment of PD-1 inhibitors in combination with chemotherapy for patients with HER2-negative advanced G/GEJC.The studies were screened out,and the relevant data were extracted to perform Meta-analysis using R 4.3.1.Results A total of five RCTs with 5297 adult patients with HER2-negative advanced G/GEJC were included,and first-line treatment with PD-1 inhibitors in combination with chemotherapy prolonged overall survival(OS)(HR=0.79,95%CI:0.74-0.85,P<0.001)and progression-free survival(PFS)(HR=0.74,95%CI:0.69-0.80,P<0.001)of patients with HER2-negative advanced G/GEJC,and improved objective response rate(ORR)(RR=1.23,95%CI:1.15-1.31,P<0.001).The results of subgroup analyses showed that for patients with combined positive score(CPS)≥1,CPS≥5,and CPS≥10,PD-1 inhibitor combined with chemotherapy as the first-line treatment regimen benefited patients in OS,PFS,and ORR and the higher the programmed death-ligand 1(PD-L1)expression,the better the efficacy.In addition,the PD-1 inhibitor combined with chemotherapy as first-line treatment regimen prolonged OS more significantly in patients with high level of microsatellite instability(MSI-H)(HR=0.35,95%CI:0.21-0.59,P<0.001).Compared with the chemotherapy group,the first-line treatment regimen by combining with PD-1 inhibitor did not increase the incidence of treatment-related adverse reactions,and the difference was not statistically significant(P>0.05).Conclusion PD-1 inhibitors in combination with chemotherapy are superior to chemotherapy as the first-line treatment for patients with advanced HER2-negative G/GEJC,and provide greater benefit for patients with high CPS or MSI-H,possessing a favorable safety profile.
作者
穆合太拜尔·海肉拉
魏瑜
张莉
Muhetaibaier Hairoua;WEI Yu;ZHANG Li(Fourth Department of General Internal Medicine/Special Needs Medicine,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;不详)
出处
《浙江医学》
CAS
2024年第14期1523-1530,共8页
Zhejiang Medical Journal
基金
新疆维吾尔自治区重点研发计划项目(2020B03003,2020B03003-3)。
关键词
晚期胃癌
胃食管交界部癌
程序性死亡受体1抑制剂
化疗
疗效
安全性
Advanced gastric cancer
Gastroesophageal junction cancer
Programmed death receptor 1 inhibitor
Chemotherapy
Efficacy
Safety
