Although tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) have a favorable and durable treatment response, almost all patients will eventually acquire resistance and develop disease progression. Re-administration of first and second-generation EGFR TKIs has been successfully executed in advanced non-small cell lung cancer (NSCLC) subsequent to EGFR-TKI resistance. However, osimertinib rechallenge following osimertinib resistance in EGFR T790M-negative patient

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... s less explored. Herein, we describe a metastatic adenocarcinoma NSCLC patient with exon 19 deletion in EGFR (19del) who acquired resistance to initial gefitinib and second-line osimertinib but was successfully rechallenged with osimertinib following treatment failure with chemotherapy. The osimertinib rechallenge, despite the absence of EGFR T790M, was considered after the development of multiple small pulmonary lesions and an increase in EGFR exon 19 deletion. After a month of osimertinib rechallenge, pulmonary and brain lesions significantly reduced achieving partial response. The success of osimertinib rechallenge following previous osimertinib resistance in a metastatic NSCLC patient with EGFR 19del in the absence of T790M suggests that re-administration of osimertinib can be a treatment option in similar situations. In addition, this case also highlights the importance of mutational profiling for treatment monitoring to understand the mutational landscape of the patient and guide subsequent treatment including treatment rechallenge.