Lung adenocarcinoma harboring triple rare EGFR exon18 mutations rapidly developed resistance to multiple therapies

Anticancer Section / Original Paper

Liu Y. · Wu Y. · Wu F. · Hu C.

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Article / Publication Details Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths worldwide. Its medical significance has spurred broad investigations into its treatment and prognosis. Shortly after the oncogenic driver mutations were identified, targeted therapies for NSCLC developed rapidly, including the discovery of tyrosine kinase inhibitors (TKIs). Epidermal growth factor receptor TKIs (EGFR-TKIs) have revolutionized the treatment era of NSCLC with common EGFR mutations, especially for non-smoking Asian women. However, it is challenging to tackle NSCLC harboring uncommon mutations, particularly the co-existence of rare EGFR mutations. Although a standard therapy has not yet been established for rare EGFR mutations, there are increasing reports of promising discoveries on the efficacy of second-generation or third-generation EGFR-TKIs on certain EGFR mutations. Here we report a female patient who was diagnosed as lung adenocarcinoma with three mutations of G724S, E709K, and V689I in exon 18. The patient responded to, but also showed rapid development of resistance to multiple therapies, including a second-generation EGFR-TKI of afatinib, a platinum based doublet chemotherapy, and a multiple target TKI of anlotinib. As such, she ended up with a short overall survival (OS) time. Further research is required to understand the resistance mechanism(s) of these complex gene mutations.

S. Karger AG, Basel

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