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

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 Gieszer et al. EGFR-VAF predicts EGFR-TKI efficacy

Systemic Inflammation Index and Tumor Glycolytic Heterogeneity Help Risk Stratify Patients with Advanced Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Treated with Tyrosine Kinase Inhibitor Therapy

“…Future prospective studies should incorporate the T790M mutation type into our scoring model. In addition, a recent study revealed that the EGFR variant allele frequency ( EGFR -aVAF) of tumor tissue can predict the benefit of TKI treatment in advanced lung adenocarcinoma [ 61 ]. Lower actionable EGFR -aVAF was correlated with unfavorable survival outcomes.…”

Novel MRPS9-ALK Fusion Mutation in a Lung Adenocarcinoma Patient: A Case Report

“…And moreover, dynamic monitoring of the mutation abundance during therapy contributes to exploring the mechanisms of resistance and predicting clinical outcomes. However, altered abundance may occur during disease progression and TKI and/or chemotherapy ( 30 ). The intratumor heterogeneity might add an extra level of difficulty to the application of mutation abundance as well, requiring detecting methods with higher sensitivity and sufficient sequencing coverage for VAF mutations capturing ( 31 , 32 ).…”

“…Cranial magnetic resonance imaging (MRI) suggested a metastatic tumor of the left parietal lobe. Therefore, she was treated with whole-brain radiotherapy (3500cGy/14F) for brain metastasis (since December 11, 2014) and four cycles of TP regimen (paclitaxel + cisplatin) chemotherapy (since January 30,2015). During therapy, she developed a headache, asthenia, poor appetite, and grade 1 nausea and vomiting, which were gradually relieved after symptomatic treatment of dehydration, lowering the intracranial pressure, antiemetics, and gastro-protection.…”

Dual driver in non-small cell lung carcinoma – therapeutic dilemma

“…High EGFR-aVAF showed significant PFS and OS benefits compared to low EGFR-aVAF. [14] ese studies imply that therapy can be individualized based on VAF, especially when dual-driver mutations/heterogeneity exist depending on the mutation with high VAF. ese hypotheses need to be validated in randomized control trials.…”