Plasma Predictive Features in Treating EGFR-Mutated Non-Small Cell Lung Cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard for EGFR-mutated non-small cell lung cancer (NSCLC).
• Treatment response varies, necessitating identification of predictive biomarkers.

Purpose of the Study:

• To investigate the impact of cell-free DNA (cfDNA) mutations and TKI plasma concentrations on progression-free survival (PFS) in EGFR-mutated NSCLC patients.

Main Methods:

• Prospective START-TKI study involving 41 patients with EGFR-mutated NSCLC treated with EGFR-TKIs.
• Next-generation sequencing (NGS) of cfDNA and measurement of plasma TKI concentrations.

Main Results:

• Patients lacking EGFR mutation plasma clearance at week 6 had significantly shorter PFS (5.5 vs. 17.0 months) and OS (14.0 vs. 25.5 months).
• Concomitant TP53 mutations at baseline were associated with shorter PFS (8.8 vs. 18.8 months) in osimertinib-treated patients.
• A decrease in erlotinib Cmean of ≥10% during treatment correlated with significantly shorter PFS (8.9 vs. 23.6 months).

Conclusions:

• Absence of EGFR mutation clearance, TP53 co-mutations, and declining erlotinib concentrations are associated with poorer outcomes in EGFR-mutated NSCLC.