Background and importance The gut microbiome plays a dominant role in modulating the therapeutic efficacy of immune checkpoint inhibitors (ICIs). The use of proton pump inhibitors (PPI) and antibiotics (ATB) can induce dysbacteriosis, which may attenuate the clinical outcomes of ICIs, as shown in previous publications.

Aim and objectives To investigate the predictive role of ATB and PPI on firstline pembrolizumab treatment in patients with metastatic non-small cell lung cancer (NSCLC) with real world data.

Material and methods Patients with metastatic NSCLC who received pembrolizumab as firstline treatment between July 2017 and January 2020 were retrospectively reviewed. Demographic data, PD-L1 expression, responses and survival rates, and other baseline variables were examined. Administration of ATB or PPI within a window of 30 days before and after the start of pembrolizumab was also collected, based on the criteria used in previous publications. Clinical outcomes were compared according to ATB or PPI co-administration.

Results 49 patients were included, 75.5% men, mean age 66.3±8.2 years, 53.1% expressed 50–75% PD-L1 and 46.9% expressed >75% PD-L1. 34.7% used ATB and 53.1% PPI. ATB compared with no ATB was associated with a shorter progression free survival (PFS) (median 12.1 vs 18.5 months, HR=0.46, 95% CI 0.20 to 1.06, p=0.068). No significant differences were observed in overall survival (OS) (HR=0.56, 95% CI 0.26 to 1.22, p=0,144). PPI compared with no PPI showed no significant differences in PFS (HR=0.98, 95% CI 0.43 to 2.21, p=0.953), but a significantly shorter OS (median 11.7 vs 17.9 months, HR=0.40, 95% CI 0.17 to 0.93, p=0.033). Multivariate analysis in all patients considering ATB, PPI, age and PD-L1 expression revealed that ATB were significantly associated with shorter PFS (HR=0.24, 95% CI 0.09 to 0.63, p=0.004) and shorter OS (HR=0.26, 95% CI 0.10 to 0.70, p=0.008). The use of PPI showed no significant differences in multivariate analysis.

Conclusion and relevance The data suggested that ATB use in patients with metastatic NSCLC may be associated with poor outcomes in terms of PFS and may influence the efficacy of pembrolizumab. The impact of PPI showed better results for OS for the group that did not receive them. These data are in line with previous publications. More studies with a larger sample of patients would be necessary to confirm these results as our limited sample size could have compromised the statistical power.

References and/or acknowledgements

1. doi:10.1093/annonc/mdy103

2. doi:10.1016/j.annonc.2020.01.006

Conflict of interest No conflict of interest