Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential prognostic biomarker tool.

e23035 Background: NSCLC patients harboring EGFR mutations are able to receive approved tyrosine kinase inhibitors (TKIs) but to better assess the treatment responses new tools are needed. Liquid biopsy is a promising one. Exosomes are the latest discovered component, containing reliable tumor informations. We performed a follow-up analysis of selected micro-RNAs (miRNAs), EGFR mutation related , in exosomes isolated from plasma of metastatic NSCLC EGFR mutated pts receiving osimertinib, in order to evaluate their potential prognostic biomarker features Methods: After ethical committee approval, for institutional study, 1 ml plasma sample of 2 EGFR positive NSCLC pts were used as exosome source for each follow-up time point during osimertinib treatment within a PK study (NCT02157883). Exosome were isolated through commercial-kit or sucrose density-gradient ultracentrifugation. After exosome characterization by Western-Blot, Transmission and Scanning Electron Microscopy, a panel of selected miRNAs (has-miR-30b-5p, 30c-5p, 221-3p, 222-3p), related to EGFR status, was analyzed. Real-Time PCR was used for miRNAs analysis and mir-1228-3p was selected as stable endogenous control. Time point before treatment was used as baseline and data were processed according to the formula 2-ΔΔct Results: Exosomes analysis is feasible in a routine clinical screening in NSCLC patients as a liquid biopsy tool. An upregulation of plasma exosomal oncomiRs (hsa-miR-221-3p/222-3p), during the first month of treatment, could predict a good clinical outcome in NSCLC patients. However, the trial was PK only and no efficacy data was collected as trial data Conclusions: A routinely non-invasive follow up of NSCLC patients during TKI treatment seems to be possible via exosomes analysis. The study of selected plasma exosomal miRNAs, related to EGFR status, could follow the disease progression during the treatment. The upregulation of oncomiRs (hsa-miR-221-3p/222-3p), correlated to a good clinical outcome, could be related to a selective exosomal disposal of oncomiRs during osimertinib treatment. Further analysis are ongoing to support these hypothesis