185P Influence of corticosteroids and antibiotics on the microbiota and the efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC)

Treatment of NSCLC has undergone important changes in recent years. The availability of immune checkpoints inhibitors (ICI) is the most relevant. It has been suggested that response to these drugs is conditioned by some host-related factors, mainly the microbiome, and the exposure to disruptive treatments, such as antibiotics or corticosteroids. Observational and prospective study, involving 55 patients (p) diagnosed with unresectable stage III or IV NSCLC receiving ICI, with at least one year follow-up and recruited between April 2019 and October 2020. Clinicopathological data, as well as faecal, saliva and blood samples were collected previous to ICI treatment. Bacterial composition of faeces and saliva was determined by 16S rDNA massive sequencing using SILVA 132 for taxonomic assignation and QIIME pipeline for statistical comparisons. Median age was 65 years.70.9% male. 65.5% ECOG 0. 50.9% of patients needed antibiotics and 58.2% used corticosteroids. Median overall survival (OS) was 19 months (m), being lower when patients received antibiotics (12 vs 23 m), but without statistical significance. By contrast, significant differences were observed in OS according to the use of corticosteroids (p = 0.011), but was not maintained in subgroups (time of use/indication). While relevant results were not found in faecal microbiota, both alfa- and beta-diversity indexes of saliva were significantly higher in patients with higher OS and ICI response. Streptococcus abundance had a negative correlation for OS, while the differential genera for those patients with optimal response to ICI was Fusobacteria and Porphyromonas. Corticosteroid exposition was associated with more Actinomyces in saliva. Regarding lymphocyte populations (CD8, CD4, CD57 …) in blood samples, with a p = 0.047, we concluded that the percentage of CD8 T lymphocytes is higher in the group without antibiotics. According to our data, corticosteroids and antibiotics intake is associated with poorer ICI treatment outcomes for NSCLC patients Interestingly, the differential bacterial composition of saliva could be used as a predictive marker of response to ICI, in particular the abundance of streptococci is significantly related to worse response and survival.