PhD Scientific Days 2022

Budapest, 6-7 July 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

Evelyn Megyesfalvi1, Judit Moldvay2, Balazs Gieszer3, Viktoria Dulai2, Judit Papay4, Ilona Kovalszky4, Jozsef Timar5, Janos Fillinger2,3, Tunde Harko2, Orsolya Pipek6, Vanda Teglasi4, Eszter Regos4, Gergo Papp4, Zoltan Szallasi7, 8, Viktoria Laszlo2,9, Ferenc Renyi-Vamos2,3, Gabriella Galffy10, Csaba Bodor4, Zsolt Megyesfalvi2,3,9*, Balazs Dome1,2,9*

1Department of Medical Oncology and Clinical Pharmacology, National Institute of Oncology, Budapest, Hungary;
2National Koranyi Institute of Pulmonology, Budapest, Hungary;
3Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary;
4Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary;
52nd Department of Pathology, Semmelweis University, Budapest, Hungary;
6Department of Physics of Complex Systems, Eotvos Lorand University, Budapest, Hungary;
7MTA-SE NAP, Brain Metastasis Research Group, Hungarian Academy of Sciences, Budapest, Hungary;
8Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA;
9Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria;
10Torokbalint County Institute of Pulmonology, Torokbalint, Hungary.
*These authors share the last authorship

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.

University and Doctoral School: Semmelweis University – Károly Rácz Doctoral School of Clinical Medicine
Supervisor: Dr. Balázs Döme