The impact of EGFR exon 19 deletion subtypes on clinical outcomes in non-small cell lung cancer

Background: The study investigated the resistant pattern and clinical outcomes of epidermal growth factor receptor (EGFR) exon 19 deletion (19del) subtypes to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). Methods: Two hundred eight treatment naive NSCLC patients detected as EGFR 19del using amplification-refractory mutation system (ARMS) were included. DNA sequencing was used to detect the subtypes. Clinicopathological features as well as patients' outcomes treated with first-line EGFR-TKIs were analyzed. Results: Thirteen EGFR 19del subtypes were confirmed in 181 samples (87.0%). Among these, delE746_A750 was the most frequent subtype (130/181, 71.8%). delE746_A750 and deletions starting from E746 were frequently found in female (P=0.003 and P=0.013, respectively) and never smokers (P=0.002 and P=0.014, respectively) than non-delE746_A750 and deletions starting from L747 patients, respectively. T790M was more frequently occurred in delE746_A750 than non-delE746_A750 (P=0.001) and deletions starting from E746 than L747 patients (P=0.006) after first-line EGFR-TKIs resistance. Patients harboring deletions starting from L747 with insertions had significantly shorter progression-free survival (PFS) than deletions starting from L747 without insertion (8.3 vs. 15.0 m, P=0.017), or all other patients (8.3 vs. 12.6 m, P=0.027). Different 19del subtypes with T790M mutation had similar PFS when treated with osimertinib (P=0.102). Conclusions: Patients with EGFR 19del subtypes had different clinicopathological features, and resistant pattern when treated with first-line TKIs. Patients harboring deletions starting from L747 with insertions had inferior outcomes than other subtypes.