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The paradigm for the pharmacological management of advanced non-small cell lung cancer (NSCLC) has been revolutionized by the development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Developing resistance to target therapy is unavoidable. Mostly, treatments for single molecular alteration after acquiring EGFR-TKI treatment resistance are well studied. However, there is limited evidence of treatment strategies for complex resistance mechanisms. Presented here is a case of an EGFR-mutated NSCLC patient who developed a complex resistance profile: T790M point mutation and EGFR amplification after first-line EGFR-TKI. This patient was safely treated with a combination of osimertinib and icotinib and achieved a significant clinical response and clear molecular response. Here we present the clinical evidence of the efficacy of osimertinib combined with icotinib in the treatment of EGFR classical mutation along with resistant mutation of T790M point mutation and EGFR amplification.

translational cancer research

Combination therapy of first and third generation EGFR-TKIs for an advanced lung adenocarcinoma patient harboring EGFR mutations and amplification: a case report