质子泵抑制剂对免疫检查点抑制剂治疗癌症患者疗效影响的Meta分析

Effects of proton pump inhibitors on the efficacy of immune checkpoint inhibitors in cancer patients: a meta-analysis

目的:系统评价质子泵抑制剂(proton pump inhibitor, PPI)的使用对免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)治疗癌症患者无进展生存期(progression free survival, PFS)和总生存期(overall survival, OS)的影响。方法:检索PubMed、Embase、Cochrane Library、Web of Science以及中国知网、维普、万方、中国生物医学文献数据库,收集自建库至2021年7月的相关研究。以风险比(hazard ratio, HR)为效应量,采用RevMan 5.3软件进行Meta分析,Stata 15.0软件进行发表偏倚分析。结果:共纳入14项回顾性队列研究,5 745例患者。Meta分析结果显示:与未使用PPI患者相比,PPI的使用降低了接受ICIs治疗癌症患者的PFS [HR=1.17,95%CI(1.02,1.35),P=0.03]和OS [HR=1.26,95%CI(1.09,1.46),P=0.001]。癌症类型亚组分析结果显示:PPI的使用降低了非小细胞肺癌(non-small cell lung cancer, NSCLC)和尿路上皮癌(urothelial carcinoma, UC)患者的PFS和OS(P<0.000 01),提高了黑色素瘤(melanoma, MM)患者的PFS(P<0.05);PPI使用时间亚组分析结果显示:ICIs前30 d使用PPI降低了患者的PFS和OS(P<0.000 01),ICIs治疗期间使用PPI提高了患者的PFS(P=0.01)。结论:在接受ICIs治疗的癌症患者中,PPI的使用与患者较差的临床结局相关。在MM患者或者ICIs治疗期间使用PPI可能与患者较好的临床结局相关,但需进一步评估。

OBJECTIVE To systematically evaluate the effects of proton pump inhibitors(PPI) on progression free survival(PFS) and overall survival(OS) of cancer patients treated with immune checkpoint inhibitors(ICIs).METHODS PubMed, Embase, Cochrane Library, Web of Science, CNKI, VIP, Wanfang, and China Biomedical literature databases were searched to collect relevant studies from inception until July 2021. Meta-analysis was performed by using RevMan 5.3 software with hazard ratio(HR) as effect size. Stata 15.0 software was used to analyze publication bias.RESULTS A total of 14 retrospective cohort studies involving 5 745 patients were included. Meta-analysis results showed that: compared with non-PPI users, PPI reduced PFS [HR=1.17, 95%CI(1.02,1.35), P=0.03] and OS [HR=1.26, 95%CI(1.09,1.46), P=0.001] of cancer patients treated with ICIs. The results of cancer subgroup analysis showed that the use of PPI reduced PFS and OS of patients with non-small cell lung cancer(NSCLC) and urothelial carcinoma(UC)(P<0.000 01), and increased PFS of patients with melanoma(MM)(P<0.05). PPI use time subgroup analysis showed that 30-day PPI use before ICIs reduced PFS and OS of patients(P<0.000 01), and the use of PPI during ICIs treatment increased PFS of patients(P=0.01).CONCLUSION Among cancer patients treated with ICIs, PPI use was associated with poorer clinical outcomes. The use of PPI in MM patients or during ICIs treatment may be associated with better clinical outcomes, but the conclusion needs further evaluation.