Risk stratification of EGFR⁺ lung cancer diagnosed with panel-based next-generation sequencing

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Next-generation sequencing (NGS) is crucial for diagnosing EGFR-mutated non-small-cell lung cancer (NSCLC).
• Risk stratification can be improved by combining molecular data with clinical parameters.

Purpose of the Study:

• To develop and validate a prognostic model for tyrosine kinase inhibitor (TKI)-treated EGFR-mutated NSCLC patients.
• To identify key predictors of progression-free survival (PFS) and overall survival (OS).

Main Methods:

• Retrospective analysis of 400 TKI-treated EGFR+ NSCLC patients.
• Validation in an independent cohort of 130 patients.
• Utilized panel-based NGS and clinical data.

Main Results:

• EGFR alterations (non-del19), TP53 co-mutations, and baseline brain metastases independently predicted PFS and OS.
• These factors combined formed the EGFR+ NSCLC risk Score (ENS), significantly differentiating patient outcomes (p < 0.001).
• Other tested parameters, including smoking, laboratory values, ECOG performance status, and histology, did not independently predict outcomes or improve the ENS model's prognostication.

Conclusions:

• EGFR variant type, TP53 status, and brain metastases are key predictors of TKI efficacy and survival in EGFR+ NSCLC.
• The ENS provides a practical and reproducible method for risk stratification in newly diagnosed metastatic EGFR+ NSCLC patients.
• This approach is effective irrespective of other currently assessed parameters.