Efficacy of tyrosine kinase inhibitors against lung cancer with EGFR exon 18 deletion: Case report and pooled analysis

Abstract

Background: Within the exon 18 of EGFR, a complex, in-frame deletion-delE709_T710ins-has been described among pulmonary adenocarcinomas with an estimated prevalence of 0.3%. Available evidences suggest that some EGFR tyrosine kinase inhibitors (TKI) have activity against this cancer. However, due to the rarity of this mutation, it remains unclear which TKI is the most effective. Methods: We reported our experience using afatinib followed by osimertinib in a patient with this mutation. We performed a systematic review of literature and conducted a pooled analysis to compare the outcomes of treatment with first generation TKIs vs. afatinib. Cases with compound mutations were excluded. Results: Our patient achieved a partial response to afatinib with a progression-free survival of 11 months. Upon disease progression, osimertinib failed to control the disease. Literature review identified 14 cases being reported: 8 received first generation TKI and 6 received afatinib. Among those with tumor response assessed, partial response occurred in 2 out of 7 patients (28.6%) treated with first generation TKI compared with 6 out of 6 patients (100%) treated with afatinib, p = 0.03. The median progression-free survival (PFS) was 3.1 months vs. 7.0 months, respectively, p = 0.005. Insufficient evidences were available to assess for the efficacy of osimertinib. Conclusion: Based on currently available data, afatinib was associated with a greater tumor response rate and a longer PFS than the first generation TKIs.

Keywords

• Tyrosine kinase inhibitor
• EGFR
• Exon 18 deletion