EGFR variant allele frequency predicts EGFR-TKI efficacy in lung adenocarcinoma: a multicenter study

Gieszer, Balazs and Megyesfalvi, Zsolt and Dulai, Viktoria and Papay, Judit and Kovalszky, Ilona and Timar, Jozsef and Fillinger, Janos and Harko, Tunde and Pipek, Orsolya and Teglasi, Vanda and Regos, Eszter and Papp, Gergo and Szallasi, Zoltan and Laszlo, Viktoria and Renyi-Vamos, Ferenc and Galffy, Gabriella and Bodor, Csaba and Dome, Balazs and Moldvay, Judit (2021) EGFR variant allele frequency predicts EGFR-TKI efficacy in lung adenocarcinoma: a multicenter study. Translational Lung Cancer Research, 10 (2). pp. 662-674. ISSN 22186751

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Abstract

Background: Although lung adenocarcinoma (LADC) with sensitizing mutations of the epidermal growth factor receptor (EGFR) is highly sensitive to EGFR tyrosine kinase inhibitors (EGFR-TKIs), in most cases disease progression inevitably occurs. Our aim was to investigate the predictive and prognostic significance of adjusted tumoral EGFR variant allele frequency (EGFR-aVAF) in the above setting. Methods: Eighty-nine Caucasian advanced-stage LADC patients with known exon-specific EGFR mutations undergoing EGFR-TKI treatment were included. The correlations of EGFR-aVAF with clinicopathological variables including progression-free and overall survival (PFS and OS, respectively) were retrospectively analyzed. Results: Of 89 EGFR-mutant LADC patients, 46 (51.7%) had exon 19 deletion, while 41 (46.1%) and 2 (2.2%) patients had exon 21- and exon 18-point mutations, respectively. Tumoral EGFR-aVAF was significantly higher in patients harboring EGFR exon 19 mutations than in those with exon 21-mutant tumors (P<0.001). Notably, patients with EGFR exon 19 mutant tumors demonstrated significantly improved PFS (P=0.003) and OS (P=0.02) compared to patients with exon 21 mutations. Irrespective of specific exon mutations, a statistically significant positive linear correlation was found between EGFR-aVAF of tumoral tissue and PFS (r=0.319; P=0.002). 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 than those with low EGFR-aVAF (P=0.011). Conclusions: Our study suggests that high (≥70%) EGFR-aVAF of tumoral tissue predicts benefit from EGFR-TKI treatment in advanced LADC and, moreover, that exon 19 EGFR mutation is associated with high EGFR-aVAF and improved survival outcomes.

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