In eSCLC, PEA Represents the Most Effective First-Line Systemic Therapy

A new standard of care for eSCLC is PEA as first-line systemic therapy. There were currently no known predictive biomarkers for pts selection.

For a single-center prospective translational study, researchers sought to  examine 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. The study was looking at eSCLC patients receiving first-line PEA. They provided preliminary GEP findings on tumor samples from a training group of eSCLC patients. The Nanostring® PanCancer IO360 panel’s analysis of 770 immune/cancer-related genes was performed using GEP. Gene expression patterns and activity and efficacy endpoints were associated. The median value was used to group the survival metrics.

There were 20 participants, and the median follow-up was 12.8 months. The median time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS) were each 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. The overall response rate was 63%. Between responders and non-responders, as well as in patients with longer vs shorter PFS, there was observed to be a difference in the expression of genes encoding costimulatory molecules and cytokines/chemokines. Genes related to cell proliferation were upregulated in responders (P=0.037), while the Notch signaling pathway was downregulated (P=0.06). Lower cytotoxic T-cells/tumor-infiltrating lymphocytes (TILs) signature scores ratio (ssr) was linked with shorter PFS (P=0.006), TTF (P=0.001), and OS (P=0.052) despite no evidence that these signature scores had any prognostic and predictive value. Better results were related with high T-cells/TILs ssr (P=0.02), mast cells/TILs ssr (P=0.003), and low macrophages/TILs ssr (P=0.04).

By using GEP analysis, they discovered immunological signatures that are prognostic and predictive in eSCLC patients following chemo-immunotherapy. The results would be validated in a larger validation sample of patients with a longer follow-up, and they would be enhanced by TME and circulating biomarker analysis.



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