The effects of antibiotics on the efficacy of immune checkpoint inhibitors in patients with non-small-cell lung cancer differ based on PD-L1 expression
The effects of antibiotics on the efficacy of immune checkpoint inhibitors in patients with non-small-cell lung cancer differ based on PD-L1 expression
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DOI：
10.1016/j.ejca.2021.02.040
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发表时间：
2021-04-07
影响因子：
8.4
通讯作者：
Kiura, Katsuyuki
中科院分区：
文献类型：
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作者：
Ochi, Nobuaki;Ichihara, Eiki;Kiura, Katsuyuki
背景：免疫检查点抑制剂（ICIs）对于包括非小细胞肺癌（NSCLC）在内的各种恶性肿瘤的治疗至关重要。最近，一些研究表明，肠道微生物组在实体癌的ICI治疗中起着重要作用，抗生素（ATB）的使用通过肠道生态失调对ICI治疗的结果产生负面影响。然而，这是否适用于NSCLC仍不清楚。ATBs对PD-L1表达的影响也尚不清楚。方法：回顾性分析2015年12月至2018年5月9所医院接受ICI单药治疗（抗pd -1或抗pd - l1抗体）的非小细胞肺癌患者的病历。在ICI治疗开始前2个月或开始后1个月使用ATBs的结果，包括无进展生存期（PFS）和总生存期（OS），使用Kaplan-Meier方法进行调查。采用Cox比例风险模型进行多因素分析。结果：本研究共纳入531例患者，其中98例（18.5%）患者在ICI治疗前后接受了ATBs。ATB的使用与较短的平均OS （ATB组为11.7个月，非ATB组为16.1个月，p = 0.028）显著相关，而PFS的差异不显著（两组均为3.5个月，p = 0.287）。接下来，我们在265例PD-L1表达确定的患者中研究了基于PD-L1表达的相关性。非小细胞肺癌和PD-L1表达患者的中位OS和PFS无显著差异，50%接受ATBs的患者的中位PFS和OS显著缩短（PFS: 4.2 vs. 9.4个月，p = 0.012; OS: 11.9 vs. 28.4个月，p = 0.011）。与整个队列相比，ATBs对PD-L1表达低于50%的NSCLC患者的影响更为显著。结论：我们的研究结果表明，在晚期NSCLC患者中，ATB使用对ICIs疗效的影响因PD-L1表达而异。使用ATB对非小细胞肺癌和PD-L1表达的患者有负面影响，但对PD-L1表达的患者没有负面影响
Background: Immune checkpoint inhibitors (ICIs) are essential for treatment of various malignancies, including non-small-cell lung cancer (NSCLC). Recently, several studies have shown that the gut microbiome plays an important role in ICI treatment of solid cancers, and antibiotic (ATB) use had a negative impact on the outcomes of ICI treatment via dysbiosis in the gut. However, whether this is applicable to NSCLC remains unclear. The impact of ATBs based on PD-L1 expression also remains unclear. Methods: We retrospectively reviewed the medical records of patients with NSCLC who received ICI monotherapy (anti-PD-1 or anti-PD-L1 antibody) at nine institutions from December 2015 to May 2018. Outcomes with use of ATBs during the 2 months before or a month after initiation of ICI treatment, including progression-free survival (PFS) and overall survival (OS), were investigated using the Kaplan-Meier method. Multivariate analysis was also conducted using a Cox proportional hazards model. Results: A total of 531 patients were included in this study, among whom 98 (18.5%) received ATBs before or after ICI treatment. ATB use was significantly associated with a shorter me-dian OS (11.7 months in the ATB group vs. 16.1 months in the non-ATB group; p = 0.028), whereas the difference in PFS was not significant (3.5 months in both the groups; p = 0.287). We next investigated the association based on PD-L1 expression in the 265 patients for whom PD-L1 expression was determined. There was no significant difference in the median OS or PFS between patients with NSCLC and PD-L1 expression 50% receiving ATBs showed significantly shorter median PFS and OS (PFS: 4.2 vs. 9.4 months, p = 0.012; OS: 11.9 vs. 28.4 months, p = 0.011). The impact of ATBs in patients with NSCLC and PD-L1 expression >50% was more significant than that in the entire cohort. Conclusions: Our results indicate that the impact of ATB use on the efficacy of ICIs differed based on PD-L1 expression in patients with advanced NSCLC. A negative impact of ATB use was found in patients with NSCLC and PD-L1 expression >50% but not in those with PD-L1 expression