Broad-Spectrum Antibiotic Regimen Affects Survival in Patients Receiving Nivolumab for Non-Small Cell Lung Cancer

Antibiotic-induced dysbiosis may affect the efficacy of immune checkpoint inhibitors. We investigated the impact of antibiotics on the clinical outcomes of nivolumab in patients with non-small cell lung cancer (NSCLC). Patients who received nivolumab for NSCLC between July 2015 and June 2018 and who were followed up until June 2020 were included in a retrospective cohort analysis. Of 140 eligible patients, 70 were on antibiotics. Overall survival (OS) was shorter in patients on antibiotics (ABX) compared to those not on antibiotics (NoABX) (p = 0.014). OS was negatively associated with piperacillin/tazobactam (PTZ) (HR = 3.31, 95% CI: 1.77-6.18), days of therapy (DOT) >= 2 weeks (HR = 2.56, 95% CI: 1.30-5.22) and DOT of PTZ. The defined daily dose (DDD) in PTZ (r = 0.27) and glycopeptides (r = 0.21) showed weak correlations with mortality. There was no difference in progression-free survival (PFS) between ABX and NoABX; however, PFS was negatively associated with the antibiotic class PTZ and DOT of PTZ. Therefore, the use of a broad-spectrum antibiotic, such as PTZ, the long-term use of antibiotics more than 2 weeks in total and the large amount of defined daily dose of specific antibiotics were associated with decreased survival in patients receiving nivolumab for NSCLC.

Automated summary

In patients with non-small cell lung cancer receiving nivolumab, the use of antibiotics, especially piperacillin/tazobactam, for more than 2 weeks, and high defined daily doses of specific antibiotics, were associated with decreased overall survival. Progression-free survival was not affected by antibiotics, but was negatively associated with certain antibiotic classes and days of therapy.