Abstract
The purpose of this study was to investigate the influence of antibiotics on the antitumor effects of immune checkpoint inhibitors (ICI) in Japanese patients with non-small-cell lung cancer (NSCLC). We enrolled 31 Japanese patients with NSCLC who received monotherapy with nivolumab, pembrolizumab, or atezolizumab at the Japan Community Health care Organization Hoshigaoka Medical Center between May 2016 and November 2019. Patients who received antibiotics from 2 months before the start of ICI treatment to 1 month after the treatment were defined as the antibiotic (+) group. The patients were divided into two groups: antibiotics (-) group (n = 13) and antibiotics (+) group (n = 18). There were no significant differences between the two groups in age, driver mutation, or number of prior treatment regimens. The median time from the start of ICI treatment to disease progression after subsequent therapy (second progression-free survival: PFS2) was significantly (P = 0.002) shorter in the antibiotics (+) group (6.0 months) than in the antibiotics (-) group (18.2 months). Furthermore, multivariate analysis showed that antibiotics (hazard ratio (HR): 4.45, 95％ confidence interval (CI): 1.33 - 14.87, P = 0.015) and a neutrophil to lymphocyte ratio ≥ 5 (HR: 3.72, 95％ CI: 1.02 - 13.59, P = 0.046) were significant risk factors for PFS2.
These results suggest that the antitumor effects of ICI are attenuated caused by the influence of antimicrobial agents on gut microbiota in Japanese patients with NSCLC.
