WCLC 2025 - Posters & ePosters-P3.12.20 VAF of EGFR Mutations in Relation to Early Tumor Shrinkage or Deepness of Response During Osimertinib in NSCLC Patients

P3.12.20 VAF of EGFR Mutations in Relation to Early Tumor Shrinkage or Deepness of Response During Osimertinib in NSCLC Patients

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This study investigated whether the variant allele frequency (VAF) of EGFR mutations correlates with tumor response parameters during osimertinib treatment in advanced non-small cell lung cancer (NSCLC) patients. VAF indicates the proportion of alleles harboring activating mutations and might influence the effectiveness of targeted therapies. <br /><br />In this retrospective exploratory analysis, 16 NSCLC patients with both common and uncommon EGFR mutations, including previously unreported compound mutations (N771Y L858R and L718V K713R L858R), were evaluated. VAF was determined via next-generation sequencing (NGS). Tumor responses were measured using Early Tumor Shrinkage (ETS), Deepness of Response (DpR) per RECIST 1.1, best tumor response (BTR), progression-free survival (PFS), and overall survival (OS).<br /><br />No significant correlation was found between VAF and either ETS (r = 0.11, p = 0.69) or DpR (r = 0.06, p = 0.83), suggesting VAF does not directly impact early or deep tumor shrinkage under osimertinib. Similarly, categorizing patients by median VAF (33%) revealed no significant difference in BTR distribution (p = 0.51). However, patients with higher VAF showed a non-significant trend toward longer median PFS (29 vs. 9 months; HR=0.55, p=0.42) and OS (36 vs. 26 months; HR=0.29, p=0.11).<br /><br />Molecular modeling indicated that the novel compound mutations do not hinder osimertinib binding, supporting its efficacy regardless of mutation complexity. The lack of significant correlation between VAF and response measures suggests osimertinib's antitumor effects may not depend on the fraction of mutated cells. Yet, higher VAF could be associated with improved survival outcomes, though this requires further validation.<br /><br />Overall, the findings imply that while VAF may not predict early or deep tumor shrinkage during osimertinib therapy, it might influence longer-term survival, highlighting the complexity of mutation profiles in therapeutic response.

Asset Subtitle

Giuseppe Bronte

Meta Tag

Speaker Giuseppe Bronte

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR mutations

variant allele frequency

VAF

osimertinib

non-small cell lung cancer

NSCLC

tumor response

early tumor shrinkage

progression-free survival

overall survival