影响肿瘤免疫检查点抑制剂疗效的伴随用药研究进展

Research progress on concomitant drugs affecting the efficacy of tumor immune checkpoint inhibitors

免疫检查点抑制剂的应用已经在各瘤种展开,成为当下研究热点。本研究总结国内外影响免疫检查点抑制剂疗效的伴随用药研究,为临床实践提供参考。以“免疫检查点抑制剂”“肿瘤”“疗效”“伴随用药”和“并发症”为关键词,检索PubMed及CNKI期刊2017-01-01-2023-06-30相关文献,纳入标准:(1)伴随用药对肿瘤免疫检查点抑制剂疗效的影响;(2)伴随用药对肿瘤免疫检查点抑制剂并发症的影响;(3)伴随用药对肿瘤免疫检查点抑制剂预后的影响。排除标准:(1)重复发表或翻译的文献;(2)质量低的文献;(3)著作和汇编以及综述类的二次文献。最终纳入文献62篇。结果显示,糖皮质激素、抗生素、质子泵抑制剂、非甾体抗炎药、二甲双胍、抗血栓药物、阿片类药物、他汀类药物和β受体阻滞剂都会不同程度地影响免疫检查点抑制剂疗效。对于抗生素、质子泵抑制剂和阿片类药物,多认为其可以通过自身直接影响或通过肠道菌群间接影响免疫检查点抑制剂使用者的预后,而且与较差的临床结局有关。对于非甾体抗炎药、糖皮质激素和抗血栓形成类药物,就目前的研究结论尚不统一。对于他汀类、二甲双胍和β受体阻滞剂则认为可能与临床结局改善有关,但这仍需要进一步研究加以验证。提示,临床常用的众多药物均可不同程度影响免疫检查点抑制剂的疗效及并发症,需要引起临床重视。但目前的研究多为小样本的回顾性研究,伴随药物对肿瘤免疫检查点抑制剂疗效的影响,仍需进行大样本、多中心的前瞻性研究验证。

At present,the application of immune checkpoint inhibitors has been carried out in various tumors and has become a research hotspot.This study summarizes the concomitant drug studies affecting the efficacy of immune checkpoint inhibitors at home and abroad,and provides a reference for clinical practice.Taking"immune checkpoint inhibitors","tumors","efficacy","concomitant medications"and"complications"as keywords,the relevant literature of PubMed and CNKI journals from January 1st,2017to June 30th,2023was searched,and the inclusion criteria were:(1)the effect of concomitant medication on the efficacy of tumor immune checkpoint inhibitors;(2)the effect of concomitant medication on the complications of tumor immune checkpoint inhibitors;(3)The effect of concomitant medication on the prognosis of tumor immune checkpoint inhibitors.Exclusion criteria:(1)duplicate published or translated literature;(2)low-quality literature;(3)secondary literature of works and compilations and reviews.Finally,62articles were included.The results showed that glucocorticoids,antibiotics,proton pump inhibitors,nonsteroidal anti-inflammatory drugs,metformin,antithrombotic drugs,opioids,statins,andβreceptor blockers all affected the efficacy of immune checkpoint inhibitors to varying degrees.Antibiotics,proton-pump inhibitors,and opioids were thought to affect the prognosis of users of immune checkpoint inhibitors directly or indirectly through their gut microbiota,and were associated with poorer clinical outcomes.For nonsteroidal anti-inflammatory drugs,glucocorticoids,and antithrombotic drugs,the current research conclusions were not uniform.Statins,metformin,andβblockers have been suggested to be associated with improved clinical outcomes,but this needs to be further researched.It is suggested that many drugs commonly used in clinical practice can affect the efficacy and complications of immune checkpoint inhibitors to varying degrees,which need to be paid clinical attention.However,most of the current studies are retrospective studies with small samples,and the effect of concomitant drugs on the efficacy of tumor immune checkpoint inhibitors still needs to be verified by large-sample,multicenter prospective studies.