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Key Points
• In this retrospective study, researchers assessed how allelic frequency relates to survival in patients with EGFR mutant non-small cell lung cancer (NSCLC). The investigators conflated allelic frequency and the presence of co-mutations, which is an established negative predictive factor for targeted therapy.
• The researchers identified all patients treated with front-line tyrosine kinase inhibitors (gefitinib, erlotinib, afatinib, osimertinib, dacomitinib) in a single center treating advanced EGFR mutated NSCLC between January 2016 and January 2020. They identified 42 patients, with 11 excluded because of unavailable variant allelic frequency data. They sequenced tumor DNA using next-generation sequencing.
• In line with the assumption that EGFR mutations are often clonal, the median allelic frequency of the EGFR mutation was 0.47 (interquartile range: 0.24-0.65). There was, however, a wide gamut among patients, with seven tumors exhibiting an allelic frequency of less than 0.2, and two tumors exhibiting an allelic frequency of less than 0.1.
• High EGFR mutation allelic frequency was related to prolonged PFS (HR 0.27, 95% 0.09-0.79, P=0.017), an association that remained even after controlling for covariates including age over 65, sex, smoking, and the use of osimertinib.
• High allelic frequency was not related to a significant difference in overall survival (HR 0.47, 95% 0.17-1.30, P=0.14).
• The authors concluded, “The mutant allelic frequency of EGFR in NSCLC appears to be associated with clinical outcomes among patients treated with TKIs. In spite of our small cohort size, we note a clear PFS improvement in patients with a high EGFR allelic frequency compared to those with a low frequency. There is a clear trend toward improved OS, though it is not significant. This predictive biomarker is independent of the generation of TKIs used and of the presence of resistance co-mutations.”

The Impact of Variant Allele Frequency in EGFR Mutated NSCLC Patients on Targeted Therapy - PubMed

The Impact of Variant Allele Frequency in EGFR Mutated NSCLC Patients on Targeted Therapy - PubMed

Source :

https://pubmed.ncbi.nlm.nih.gov/33869038/

EGFR mutations represent the most common currently targetable oncogenic driver in non-small cell lung cancer. There has been tremendous progress in targeting this alteration over the course of the last decade, and third generation tyrosine kinase inhibitors offer previously unseen survival rates amo ...