Exon 19 Insertions: Do Patients Respond to Tyrosine Kinase Inhibitor Treatment?

Background/aim: Epidermal growth factor receptor (EGFR) exon 19 insertions are very rare mutations and their response to tyrosine kinase inhibitors (TKIs) is uncertain. We report our experience concerning two patients, along with a literature review.

Patients And Methods: A total of 1,046 non-small-cell lung cancer tumor tissue samples were screened for EGFR mutations, using direct sequencing or next-generation sequencing. Two patients presented the same insertion of 18 nucleotides in EGFR exon 19 and were treated with afatinib.

Results: Both patients responded to afatinib, showing a stable disease (SD) and a progression-free survival (PFS) of 6 and 10 months along with an overall survival (OS) of 17 and 19 months, respectively. A review of the literature data concerning clinical responsiveness to different generations of TKIs in patients with EGFR exon 19 insertions, including data of our two patients (n=28), showed a response rate of 64% and disease control rate of 92%. The calculated median PFS for the 28 cases, independently of the TKIs administered, was 9 months; median OS (n=15) was 13 months. Median PFS for patients receiving gefitinib and erlotinib was 9 months and 12.5 months, respectively, consistent with the median PFS observed in patients with "classical" EGFR mutations, treated with these agents.

Conclusion: Patients with EGFR insertions in exon 19 have demonstrated sensitivity to treatment with EGFR TKIs, suggesting that patients carrying these mutations should be treated with these inhibitors.