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

被引：46

作者：

Ochi, Nobuaki ^{[1
]}

Ichihara, Eiki ^{[2
]}

Takigawa, Nagio ^{[1
]}

Harada, Daijiro ^{[3
]}

Inoue, Koji ^{[4
]}

Shibayama, Takuo ^{[5
]}

Hosokawa, Shinobu ^{[6
]}

Kishino, Daizo ^{[7
]}

Harita, Shingo ^{[8
]}

Oda, Naohiro ^{[9
]}

Hara, Naofumi ^{[10
]}

Hotta, Katsuyuki ^{[11
]}

Maeda, Yoshinobu ^{[10
]}

Kiura, Katsuyuki ^{[2
]}

机构：

[1] Kawasaki Med Sch, Dept Gen Internal Med 4, Okayama, Japan

[2] Okayama Univ Hosp, Dept Allergy & Resp Med, Okayama, Japan

[3] Natl Hosp Org, Dept Thorac Oncol, Shikoku Canc Ctr, Shikoku, Ehime, Japan

[4] Ehime Prefectural Cent Hosp, Dept Resp Med, Matsuyama, Ehime, Japan

[5] Natl Hosp Org, Dept Resp Med, Okayama Med Ctr, Okayama, Japan

[6] Japanese Red Cross Okayama Hosp, Dept Resp Med, Okayama, Japan

[7] Himeji Red Cross Hosp, Dept Resp Med, Himeji, Hyogo, Japan

[8] Okayama Saiseikai Gen Hosp, Dept Internal Med, Okayama, Japan

[9] Fukuyama City Hosp, Dept Internal Med, Fukuyama, Hiroshima, Japan

[10] Okayama Univ, Dept Hematol Oncol & Resp Med, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[11] Okayama Univ Hosp, Ctr Innovat Clin Med, Okayama, Japan

来源：

EUROPEAN JOURNAL OF CANCER | 2021年 / 149卷

关键词：

Anti-PD-1; antibody; Anti-PD-L1; Antibiotics; Immune checkpoint inhibitor; PD-L1; expression; MICROBIOME; DOCETAXEL; NIVOLUMAB; BLOCKADE; IMPACT;

D O I：

10.1016/j.ejca.2021.02.040

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 and those not receiving ATBs (PFS: 3.3 vs. 2.8 months, p = 0.88; OS: 9.5 vs. 17.1 months, p = 0.24). Conversely, 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 <50%. (c) 2021 Elsevier Ltd. All rights reserved.

引用

页码：73 / 81

页数：9

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