GENE EXPRESSION PROFILES (GEP), INCLUDING IFN-GAMMA AND TUMOR INFLAMATION SIGNATURE (TIS), AS PREDICTORS OF ADVANCED NSCLC RESPONSE TO IMMUNE CHECKPOINT INHIBITORS

Background: Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of advanced non-small-cell lung cancer (aNSCLC), however, it is still necessary to improve the selection of patients for this therapeutic modality. Gene expression profile (GEP) is a promising way to evolve in this field. The aim of this study was to assess the predictive value of different genetic signatures, including Tumor Inflamation Signature (TIS) and Interferon-gamma (IFN-y). Methods: This is a retrospective cohort of Brazilian aNSCLC patients treated with ICIs in any line. Clinical data were collected from medical records. Total RNA was extracted from FFPE tumor tissue. GEP was assessed using the nCounter PanCancer IO360 panel (NanoString Technologies), which comprises 770 genes involved in the cancer immune response and 48 known genetic signatures. Results: 135 patients were included. The median age was 61 years old, most of them were male (57.8%), had a history of smoking (83.6%), ECOG-PS 0-1 (88.7%), clinical stage IV (91.9%) and adenocarcinoma was the predominant histology (65.1%). As treatment, 40.7% received ICI in first. With a median follow-up of about 28 months, the median overall survival after starting immunotherapy (post-immunotherapy survival – PIS) was 17.8 months and median real-world progression-free survival (rwPFS) was 5.5 months. After several filters 66 patients were included in the gene expression profile analysis. 14 different previously described signatures were associated with PIS (IDO1, PD-L2, Cytotoxicity, Cytotoxic Cells, IFN Downstream, CTLA4, PD-L1, TIGIT, Lymphoid, Immunoproteasome, Exhausted CD8, IFN Gamma, TIS and APM). TIS and IFN-y were the signatures that had the greater statistical significance. The median PIS for patients with high TIS expression was 29.2 months versus 15.5 months (HR 0.42; 95%CI; 0.17-0.67; p<0.05) for those with low expression. Similar results were observed for IFN-y. Conclusions: Fourteen genetic signatures have been linked to survival in patients with NSCLC treated with immunotherapy, including signatures known as IFN-y and TIS.