The Prognostic Significance of EGFR Adjusted Variant Allele Frequency on First-Line Osimertinib Efficacy in Advanced EGFR-Mutant NSCLC.

Introduction: The prognostic significance of EGFR variant allele frequency (VAF) remains unclear in advanced EGFR-mutant (EGFR-mt) NSCLC. We examined the relationship of EGFR VAF and clinical outcomes in patients treated with first-line osimertinib. Methods: This retrospective cohort study evaluated patients with advanced EGFR-mt NSCLC treated at the Ottawa Hospital between July 2021 and June 2023. Baseline characteristics were collected from electronic medical records. Adjusted VAF (aVAF) was calculated by normalizing EGFR VAF to tumor cellularity and analyzed according to predefined thresholds: aVAF < 50% (low) and aVAF > 100% (high). The primary outcome was progression-free survival (PFS). Results: Of 141 patients diagnosed with EGFR-mt NSCLC, 59 were included. The median age was 70 years, and 70% were females. There were 23 (39.0%) cases with low aVAF and 16 (27.1%) with high aVAF. Neither aVAF < 50% (HR = 1.01; p = 0.76) or aVAF > 100% (HR = 0.81; p = 0.57) was associated with PFS. However, ECOG performance status ≥ 2 (vs 0-1; HR = 3.63, p < 0.001), EGFR exon 19 deletion (vs. L858R; HR = 0.50, p = 0.021), and liver involvement (HR = 2.65, p = 0.005) were associated with PFS on multivariable analysis. Discussion: EGFR aVAF was not associated with clinical outcomes. However, established prognostic factors including ECOG performance status, EGFR mutation subtype, and liver involvement were associated with PFS.