2024 World Conference on Lung Cancer (WCLC) - Posters-P2.11B.01 Deciphering Immunotherapy Resistance Mechanisms in Metastatic NSCLC, Insights from Plasma Proteomics Analysis

P2.11B.01 Deciphering Immunotherapy Resistance Mechanisms in Metastatic NSCLC, Insights from Plasma Proteomics Analysis

Pdf Summary

Itamar Sela's research at OncoHost focuses on deciphering immunotherapy resistance mechanisms in metastatic non-small cell lung cancer (NSCLC) through plasma proteomic analysis. The study introduces the PROphetNSCLC test, which uses machine learning to analyze plasma protein expressions and identify Resistance Associated Proteins (RAPs) that predict clinical benefit from treatment. Initially assessing 7,000 proteins, the test identifies 388 RAPs with notable expression differences between patients who respond to treatment (CB) and those who do not (NCB).<br /><br />Each RAP serves as an indicator, being either "on" or "off," forming an individualized resistance map. This map helps infer clinical benefits and resistance pathways. The study's model, tested through a blinded validation cohort, demonstrates a high correlation between predicted and observed clinical benefits. Patients with a "positive" PROphet result are associated with a significant survival advantage, having a median overall survival (OS) of 25.9 months compared to 10.8 months for "negative" ones.<br /><br />The research highlights the clinical utility of the PROphetNSCLC test as a composite biomarker, showing varied median OS rates despite patients receiving the same treatment. PROphet-positive patients gain durable benefits from PD-(L)1 inhibitors alone, while negative results predict poor outcomes with monotherapy. The study underscores the importance of plasma proteomics in identifying key biological processes and enhancing the precision of treatment strategies through personalized medicine.<br /><br />Sela's work advocates for the wider application of proteomics in clinical settings, suggesting it could improve the effectiveness of first-line therapeutic decisions for mNSCLC patients by translating proteomic data into actionable insights for treatment plans.

Asset Subtitle

Itamar Sela

Meta Tag

Speaker Itamar Sela

Topic Metastatic NSCLC – Immunotherapy

Keywords

immunotherapy resistance

metastatic non-small cell lung cancer

plasma proteomic analysis

PROphetNSCLC test

machine learning

Resistance Associated Proteins

personalized medicine

clinical benefits

survival advantage

proteomics