Abstract 1277P
Background
While immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced non-small cell lung cancer (NSCLC), the identification of reliable predictive factors is still a partially unmet need. Numerous studies have shown the potential of miRNAs as biomarkers for diagnosis, prognosis, and prediction of response to therapy. Tumor-derived miRNAs have been identified in several body fluids and within extracellular vesicles such as exosomes (Exo). We aimed at identifying a prognostic signature of Exo-miRNAs in NSCLC patients treated with nivolumab.
Methods
We included 174 patients who received nivolumab in second or subsequent lines. For each, a plasma sample was collected at baseline to isolate Exo-miRNAs that were profiled using the agilent microarray platform, containing 2,549 miRNAs. Patients were then randomly divided for 10 times into a training (n=125) and a validation (n=49) set, and 10 penalized Cox regression models using the LASSO method were built on each different training set and applied to the corresponding validation sets.
Results
Overall, 82 patients (47.3%) underwent at least two treatment lines before nivolumab. The miRNome profile identified two miRNAs (miR-208a-5p and miR-574-5p) overexpressed in patients with a survival time lower than 9 months (adjusted p-value=0.03) that were consistently retained by the penalized Cox regression models and were positively associated with poor survival in each validation set. Notably, by dividing the total cohort of patients into two groups according to the median value of the combined expression of the two Exo-miRNAs, the overall survival Kaplan-Meier curves were significantly different (p-value=0.0001). The in-silico prediction of the genes targeted by the two miRNAs suggested two main pathways already described in ICI resistance mechanisms: the TGF beta and the antigen processing and presentation pathways.
Conclusions
Our miRNome profile identified 2 miRNAs that could serve as a signature to identify NSCLC patient subgroups with different benefits from nivolumab. This study was supported by Bristol-Myers Squibb (CA209-828-BMS) and the Italian Ministry of Health (CO-2016-02361470).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bristol-Myers Squibb; Italian Ministry of Health.
Disclosure
C. Genova: Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Boehringer Ingelheim; Honoraria (self): MSD; Honoraria (self): Roche. All other authors have declared no conflicts of interest.