PhD Scientific Days 2022

Pathology and Oncology I. (Poster discussion will take place in the Aula during the Coffee Break)

EGFR-TKI Efficacy according to Tumoral EGFR Variant Allele Frequency in Advanced Stage Lung Adenocarcinoma Patients

Text of the abstract

Introduction: Sensitizing mutations of the epidermal growth factor receptor (EGFR) in lung adenocarcinoma (LADC) confer sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs). Despite precise patient selection, the efficacy of TKIs is not consistent for every individual.

Aims: Our goal was to investigate the predictive and prognostic significance of adjusted tumoral EGFR variant allele frequency (EGFR-aVAF) in advanced-stage LADC patients.

Method: A total of 89 Caucasian LADC patients with known exon-specific EGFR mutations were included in the current study who received EGFR-TKI treatment. The correlations of EGFR-aVAF with clinicopathological variables including progression-free and overall survival (PFS and OS, respectively) were retrospectively analyzed.

Results: Overall, 46 (51.7%) patients were diagnosed with exon 19 deletions, while 41 (46.1%) and 2 (2.2%) patients had exon 21- and exon 18-point mutations, respectively. Patients with EGFR exon 19 mutation showed significantly higher tumoral EGFR-aVAF compared to those with exon 21 mutation (P<0.001). Our data showed significantly improved PFS (P=0.003) and OS (P=0.02) in EGFR exon 19 (vs. exon 21) mutant tumors. Regardless of exon mutation subtype a statistically significant positive linear correlation was found between EGFR-aVAF of tumoral tissue and PFS (r=0.319; P=0.002). Importantly, high (≥70%) EGFR-aVAF was an independent predictor of longer PFS [vs. low (<70%) EGFR-aVAF; median PFSs were 52 vs. 26 weeks, respectively; P<0.001]. Additionally, patients with high EGFR-aVAF also had significantly improved OS compared to those with low EGFR-aVAF (P=0.011).

Conclusion: Our results suggest that EGFR-aVAF of tumoral tissue predicts the extent of benefit from EGFR-TKI treatment. Moreover, we also show that the average EGFR-aVAF is higher among patients with exon 19 deletions thus confirming the longer PFS and OS of these patients.

e-mail: paszkan.evelynkatalin@gmail.com
University and Doctoral School: Semmelweis University – Károly Rácz Doctoral School of Clinical Medicine
Supervisor: Dr. Balázs Döme