Abstract 781: Pretreatment immune-related gene expression analysis predicts survival of patients with metastatic lung cancer treated with anti PD-1 antibody
Authors: Tagliamento Marco , Sommariva Sara , Campi Cristina , De Luca Giuseppa , Bello Maria Giovanna Dal , Mora Marco , Coco Simona , Dono Mariella , Genova Carlo 
Published: June 2022

Introduction: Antibodies targeting PD-1 play a relevant role in the management of metastatic non-small cell lung cancer (NSCLC), although the majority of patients experience disease progression to treatment. We performed a pretreatment immune-related gene expression analysis to predict outcomes of patients with advanced stage NSCLC receiving pembrolizumab as first-line therapy.

Methods: Pretreatment tissue samples from 48 metastatic NSCLC patients with PD-L1 high expression (&gt; 50% 22C3 clone testing antibody), who undergone first line pembrolizumab therapy, were evaluated. Total RNA was isolated (RNeasy FFPE Kit Qiagen) and quantified (NanoDrop Fluorometer, Thermo Fisher Sci.). We performed a mRNA expression analysis of 770 immune-related genes (belonging to 21 pathways) by using the nCounter PanCancer Immune Profiling Panel (NanoString Tech.). Data normalization was performed in-house by using R functions. Patients were clustered by the K-means algorithm according to results of the gene expression analysis for each pathway. Advanced analyses were performed by nCounter Advanced Analysis plug in for nSolver Software (v. 2.0.134) and R package. Estimates of Overall Survival (OS) were done by Kaplan-Meier curves and tests of differences by log-rank test. Regression models were built including covariables. All tests were two-sided, with a statistical significance at p-value &lt; 0.05.

Results: The median age of patients was 72.5 years (IQR 64.3-77.0). Thirty-seven (77.1%) were male, 36 (75%) with non-squamous histology, 37 (77.1%) had an ECOG PS of 0 or 1, and 46 (95.8%) were former or current smokers. In 16 out of 48 cases (33.3%) the immune profile was performed on tumor-infiltrated lymph nodes. Disease Control Rate per RECIST 1.1 was 52.1% (16 partial and 2 complete responses, 7 disease stabilizations as best response). Median Progression-Free Survival was 2.96 months (95% CI 2.35-7.25), median OS was 13.43 months (95% CI 6.24-NR). The principal component analysis excluded 1 outlier subject by the gene expression analysis. Five gene expression signatures were significantly correlated with OS (Adhesion, Cytokines, Leukocyte Functions, Macrophage Functions, TNF Superfamily), all identifying 2 clusters of patients among each pathway. The 8-genes signature of the Leucocyte Functions pathway (CX3CL1, FUT7, HCK, IFNG, LCP1, SH2D1B, THBD, VEGFA) was the solely significantly correlated to OS regardless of age, sex, tumor histology, ECOG PS, smoke and site of diagnostic sampling (lymph node or non-nodal tissue), with a Hazard Ratio between the identified clusters of 0.29 (95% CI 0.24-0.60, p = 0.01).

Conclusions: Our results support the hypothesis that pretreatment immune-related mRNA expression patterns, identified through the nCounter platform, may predict OS of patients with metastatic NSCLC treated with first line anti PD-1 therapy.

Citation Format: Marco Tagliamento, Sara Sommariva, Cristina Campi, Giuseppa De Luca, Maria Giovanna Dal Bello, Marco Mora, Simona Coco, Mariella Dono, Carlo Genova. Pretreatment immune-related gene expression analysis predicts survival of patients with metastatic lung cancer treated with anti PD-1 antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 781.