Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-sensitive Exon 19 Insertion and Exon 20 Insertion in Patients With Advanced Non-Small-cell Lung Cancer

Abstract

Background: The clinical responsiveness to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with exon 19 insertion and the specific exon 20 insertion (A763_Y764 insFQEA) are still not well known.

Materials and methods: We analyzed cancer specimens taken from NSCLC patients for EGFR mutations using RNA reverse transcription polymerase chain reaction or direct DNA sequencing. The clinical course and responsiveness to an EGFR TKI in patients with EGFR exon 19 insertion or exon 20 insertion (A763_Y764 insFQEA) were recorded. The published data regarding these mutations were also reviewed.

Results: From September 1995 to May 2015, we found 4 patients with an EGFR exon 19 insertion and 6 patients with an EGFR exon 20 insertion (A763_Y764 insFQEA) at the National Taiwan University Hospital. Among patients with an exon 19 insertion, 3 received an EGFR TKI. Of the 3 patients, 1 had a partial response, 1 had stable disease, and 1 had progressive disease. Of the 6 patients with the exon 20 insertion (A763_Y764 insFQEA), 3 received an EGFR TKI. Of those 3 patients, 2 had a partial response and 1 had progressive disease. A review of the published data, together with the data from our patients, patients with an exon 19 insertion and treated with an EGFR TKI (n = 18) had a response rate of 56% and a median time to progression of 10.4 months. Patients with the exon 20 insertion (A763_Y764 insFQEA) and treated with an EGFR TKI (n = 11) had a response rate of 73% and a median time to progression of 5.0 months.

Conclusions: Advanced NSCLC bearing the EGFR exon 19 insertion or exon 20 insertion (A763_Y764 insFQEA) is sensitive to EGFR TKIs.

Keywords: A763_Y764 insFQEA; EGFR mutation; I744_K745 insKIPVAI; NSCLC; Uncommon mutation.