Abstract 19P
Background
First-line systemic treatment with PEA is a new standard of care for eSCLC. No predictive biomarkers for pts selection have been identified so far.
Methods
This is a single-center prospective translational study on eSCLC pts receiving first-line PEA, investigating the predictive value of circulating (cell-free DNA Next Generation Sequencing, microRNA profile and Telomerase Reverse Transcriptase -TERT- mRNA levels) and tissue (tumor microenvironment, TME; GEP and proteomics analyses) biomarkers. We report preliminary data of GEP on tumor samples in a training set of eSCLC pts. GEP was performed analyzing 770 immune/cancer-related genes by the Nanostring® PanCancer IO360 panel. Gene expression signatures were correlated with activity and efficacy endpoints. Survival measures were categorized according to median value.
Results
Twenty pts were included; median follow-up was 12.8 months. Overall response rate was 63%, median time to treatment failure (TTF), progression free (PFS) and overall survival (OS) were 5.0 (95%CI, 3.9-6.1), 5.0 (95%CI, 3.9-6.1) and 7.2 months (95%CI, 7.1 -7.4), respectively. A differential expression of genes encoded for costimulatory molecules and cytokines/chemokines was reported between responders and non-responders and in pts with longer versus shorter PFS. Responders showed upregulation of cell proliferation genes (p=0.037) and downregulation of the Notch signaling pathway (p=0.06). While no prognostic and predictive impact of the absolute CD8+ T-cells and cytotoxic T-cells signature scores was evidenced, lower cytotoxic T-cells/tumor-infiltrating lymphocytes (TILs) signature scores ratio (ssr) was associated with shorter PFS (p= 0.006), TTF (p=0.001) and OS (p=0.052). High T-cells/TILs ssr (p=0.02), mast cells/TILs (p=0.003) ssr and low macrophages/TILs ssr (p=0.04) were associated with better outcome.
Conclusions
We identify predictive and prognostic immune signatures in eSCLC receiving chemo-immunotherapy through GEP analysis. These data will be confirmed in a wider validation set of pts with a longer follow-up and complemented with TME and circulating biomarkers analyses.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
University of Padua.
Funding
University of Padua.
Disclosure
L. Bonanno: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal and Institutional, Invited Speaker: AstraZeneca. V. Guarneri: Financial Interests, Personal, Advisory Board: Roche, Eli Lilly, Novartis, MSD, Gilead; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck. G. Pasello: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Principal Investigator: Amgen, AstraZeneca, Roche, Eli Lilly, Novartis; Financial Interests, Institutional, Funding: AstraZeneca, Roche. All other authors have declared no conflicts of interest.