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Published on: August 11, 2017
EGFR variant allele frequency predicts EGFR-TKI efficacy in lung adenocarcinoma: a multicenter study
Balazs Gieszer1, Zsolt Megyesfalvi1,2,3, Viktoria Dulai2
1Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary.
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.
Insights
High adjusted tumoral epidermal growth factor receptor variant allele frequency (EGFR-aVAF) predicts better outcomes for lung adenocarcinoma (LADC) patients treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). Specifically, EGFR exon 19 mutations are linked to higher EGFR-aVAF and improved progression-free and overall survival.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung adenocarcinoma (LADC) with sensitizing epidermal growth factor receptor (EGFR) mutations shows initial sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKIs).
- However, acquired resistance frequently leads to disease progression, necessitating identification of predictive biomarkers.
- The prognostic and predictive value of adjusted tumoral EGFR variant allele frequency (EGFR-aVAF) remains to be fully elucidated.
Purpose of the Study:
- To investigate the predictive and prognostic significance of EGFR-aVAF in advanced LADC patients treated with EGFR-TKIs.
- To determine the correlation between EGFR-aVAF and specific EGFR mutations (exon 19 vs. exon 21).
- To assess the association of EGFR-aVAF with progression-free survival (PFS) and overall survival (OS).
Main Methods:
- Retrospective analysis of 89 Caucasian advanced-stage LADC patients with known EGFR mutations receiving EGFR-TKI treatment.
- Correlation analysis of EGFR-aVAF with clinicopathological variables, PFS, and OS.
- Comparison of EGFR-aVAF and survival outcomes between patients with EGFR exon 19 and exon 21 mutations.
Main Results:
- EGFR exon 19 mutations were associated with significantly higher tumoral EGFR-aVAF compared to exon 21 mutations (P<0.001).
- Patients with exon 19 mutations showed significantly improved PFS (P=0.003) and OS (P=0.02) versus those with exon 21 mutations.
- High EGFR-aVAF (≥70%) independently predicted longer PFS (median 52 vs. 26 weeks, P<0.001) and improved OS (P=0.011) irrespective of mutation type.
Conclusions:
- High tumoral EGFR-aVAF (≥70%) is a significant predictor of treatment benefit from EGFR-TKIs in advanced LADC.
- EGFR exon 19 mutations are associated with higher EGFR-aVAF and favorable survival outcomes.
- EGFR-aVAF serves as a valuable biomarker for predicting response and prognosis in EGFR-mutated LADC.
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