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

Nobuaki Ochi, Eiki Ichihara, Nagio Takigawa, Daijiro Harada, Koji Inoue, Takuo Shibayama, Shinobu Hosokawa, Daizo Kishino, Shingo Harita, Naohiro Oda, Naofumi Hara, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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 median 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%.

Original languageEnglish
Pages (from-to)73-81
Number of pages9
JournalEuropean Journal of Cancer
Volume149
DOIs
Publication statusPublished - May 2021

Keywords

  • Antibiotics
  • Anti–PD-1 antibody
  • Anti–PD-L1 antibody
  • Immune checkpoint inhibitor
  • PD-L1 expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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