Introduction: This study investigates the impact of variant allele frequency (VAF) of EGFR mutations on osimertinib effectiveness in mNSCLC. Despite NGS provides extensive genomic data, VAF is poorly used in clinical practice. This research explores the relationship between VAF and ETS or DpR. Methods: We retrospectively analyzed mNSCLC patients treated with an EGFR-TKI; VAF was determined by NGS. The primary goal was to explore the relationship between VAF and ETS or DpR, according to RECIST-1.1 criteria. Secondary objectives included assessing associations between VAF and best tumor response (BTR), progression-free survival (PFS), and overall survival (OS). Molecular modeling was performed for compound uncommon mutations, never described before in literature. Statistical analyses included Spearman correlation, chi-squared test, and log-rank test. Results: Sixteen patients were included. No signi cant correlation between VAF and ETS (r= 0.11, p= 0.69) (Figure 1A) or DpR (r=0.06, p= 0.83) (Figure 1B) were found. A VAF percentage equal to or greater than the median (33%) showed a trend toward longer median PFS (29 months vs. 9 months; HR: 0.55, p= 0.42) and OS (36 months vs. 26 months; HR: 0.29, p= 0.11), though not statistically signi cant. We found undescribed compound uncommon EGFR mutations: N771Y + L858R and L718V + K713R + L858R. These mutations do not prevent osimertinib binding and function, as suggested by molecular modeling (Figure 2). Conclusions: VAF of EGFR mutations does not significantly in uence tumor size reduction (ETS/DpR) in osimertinib-treated patients. Higher VAF showed a not statistically signi cant trend toward improved PFS and OS.
P3.12.20 VAF of EGFR Mutations in Relation to Early Tumor Shrinkage or Deepness of Response During Osimertinib in NSCLC Patients
Carnevale, A.;Ciancetta, A.;Cosi, D. M.;Fragale, C.;Ciarrocchi, S.;Di Guglielmo, M. L.;Tinelli, G.;Mindicini, N.;Battara, L.;D'Abundo, L.;Gafà, R.;
2025
Abstract
Introduction: This study investigates the impact of variant allele frequency (VAF) of EGFR mutations on osimertinib effectiveness in mNSCLC. Despite NGS provides extensive genomic data, VAF is poorly used in clinical practice. This research explores the relationship between VAF and ETS or DpR. Methods: We retrospectively analyzed mNSCLC patients treated with an EGFR-TKI; VAF was determined by NGS. The primary goal was to explore the relationship between VAF and ETS or DpR, according to RECIST-1.1 criteria. Secondary objectives included assessing associations between VAF and best tumor response (BTR), progression-free survival (PFS), and overall survival (OS). Molecular modeling was performed for compound uncommon mutations, never described before in literature. Statistical analyses included Spearman correlation, chi-squared test, and log-rank test. Results: Sixteen patients were included. No signi cant correlation between VAF and ETS (r= 0.11, p= 0.69) (Figure 1A) or DpR (r=0.06, p= 0.83) (Figure 1B) were found. A VAF percentage equal to or greater than the median (33%) showed a trend toward longer median PFS (29 months vs. 9 months; HR: 0.55, p= 0.42) and OS (36 months vs. 26 months; HR: 0.29, p= 0.11), though not statistically signi cant. We found undescribed compound uncommon EGFR mutations: N771Y + L858R and L718V + K713R + L858R. These mutations do not prevent osimertinib binding and function, as suggested by molecular modeling (Figure 2). Conclusions: VAF of EGFR mutations does not significantly in uence tumor size reduction (ETS/DpR) in osimertinib-treated patients. Higher VAF showed a not statistically signi cant trend toward improved PFS and OS.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
