质子泵抑制剂对免疫检查点抑制剂治疗原发性肝癌疗效的影响

Effect of proton pump inhibitors on the efficacy of immune checkpoint inhibitors in the treatment of primary liver cancer

目的 探究质子泵抑制剂(PPI)对接受免疫治疗的肝癌患者临床结果的影响。方法 收集接受过免疫治疗的原发性肝癌患者信息,经过筛选后纳入215例患者进行回顾性研究分析。使用χ^(2)检验、秩和检验、Kaplan-Meier方法和COX回归对数据进行统计分析,比较免疫治疗前后30 d内使用PPI组与未使用PPI组的无进展生存期(PFS)、疾病控制率(DCR)和总生存期(OS)。结果 生存分析表明使用PPI组和未使用PPI组在PFS(P=0.679)和OS(P=0.887)上差异无统计学意义,单因素和多因素分析显示PPI的使用不是降低PFS(单因素HR=1.341;95%CI:0.950~1.894;多因素HR=1.334;95%CI:0.934~1.906)、OS(单因素HR=1.307;95%CI:0.647~2.638;多因素HR=1.09;95%CI:0.524~2.301)、DCR(单因素OR=0.778;95%CI:0.387~1.562;多因素OR=0.830;95%CI:0.398~1.732)的危险因素。结论 在免疫治疗前后30 d内使用PPI对晚期原发性肝癌患者免疫治疗的疗效没有不良影响。

Objective To investigate the effect of proton pump inhibitor(PPI) on the clinical outcome of liver cancer patients receiving immunotherapy. Methods The data of patients with primary liver cancer who had received immunotherapy was collected. After screening, 215 patients were included for retrospective study and analysis. The χ^(2) test, rank sum test, Kaplan-Meier method and Cox regression were used to statistically analyze the data. The progression free survival(PFS), disease control rate(DCR) and overall survival(OS) of PPI group and non PPI group within 30 days before and after immunotherapy were compared. Results Survival analysis showed that there was no significant difference in PFS(P=0.679) or OS(P=0.887) between PPI group and non PPI group. Univariate and multivariate analysis showed that PPI use did not reduce PFS(univariate HR, 1.341;95% CI, 0.950-1.894;multivariate HR, 1.334;95% CI, 0.934-1.906), OS(univariate HR, 1.307;95% CI, 0.647-2.638;multivariate HR, 1.09;95% CI, 0.524-2.301) or DCR(univariate OR, 0.778;95% CI, 0.387-1.562;multivariate OR, 0.830;95% CI, 0.398-1.732). Conclusion The use of PPI within 30 days before and after immunotherapy has no adverse effect on the efficacy of immunotherapy in patients with advanced primary liver cancer. It needs to be further confirmed by more systematic analysis.