A Rare Presentation of a Non-Asian Female With Metastatic Non-small-cell Lung Cancer Harboring EGFR L747P Mutation With Clinical Response to Multi-targeted Epigenetic and EGFR Inhibition

Background: Activating mutations of the epidermal growth factor receptor (EGFR) gene have been utilized to predict the effectiveness of EGFR tyrosine kinase inhibitor (TKI) therapy. The most common EGFR mutations are exon 19 deletion and exon 21-point mutation, which are sensitive to EGFR TKI. However, rare/complex EGFR mutations still exist, data of which are scarce and controversial. Hence, their role in response to standard therapy remains uncertain. Case Report: We present the case of a patient diagnosed with stage IV lung adenocarcinoma for whom standard chemotherapies, including platinum agents, had failed. The patient was found to have an EGFR exon 19 (L747P) mutation, as evident in her liquid biopsy. This alteration has not been described before in the literature on non-Asian females. Data from the current case study highlight the aggressive nature of this type of EGFR mutation as indicated by the complete resistance to erlotinib. Using standard first-generation EGFR inhibitors in treating this point mutation was considered inadequate. However, this patient showed a substantial response when treated with erlotinib combined with epigenetic therapies, consisting of DNA methyltransferase and histone deacetylase inhibitors. For more than 8 years, the patient has been responding to combination therapy with a normal quality of life. Conclusion: This case represents a possible novel approach to reducing resistance in patients harboring this rare EGFR mutation which may translate to better outcomes.