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Background  Endothelial growth factor receptor ( EGFR ) mutations are an essential driver of personalized therapy for patients with lung cancer and are detected in approximately 15% of Caucasian and 50% of Asian patients.  EGFR  tyrosine kinase inhibitors have been developed and used for this set of patients. T790M mutation in exon 20 is usually associated with secondary resistance to  EGFR  tyrosine kinase inhibitors therapy but is also present in treatment-naïve patients. The frequency for baseline T790M mutation varies from 4 to 35% according to the detection method used. Newer techniques have yielded higher rates, but concerns about false-positive results have been raised. Compound mutations account for 4–14% of all  EGFR -mutated tumors, with no studies yet to provide a frequency rate for T790M + 19 deletion association due to the small number of cases. However, there are reports that pretreatment T790M + L858R association is significantly more frequent compared to T790M + exon 19 deletion mutations. Diagnostic challenges, current knowledge on the subject, and therapeutic decisions are discussed.    Case presentation  We present the case of a 43-year-old Hispanic woman, a treatment-naïve patient, with metastasized lung cancer adenocarcinoma harboring a T790M deletion along with the classic 19 mutation. The initial symptoms were monoparesis of her left leg, associated with hyperreflexia, and hypoesthesia. In the absence of third-generation tyrosine kinase inhibitors, a platinum-based therapy was initiated with no response and she died 4 months after diagnosis.    Conclusions  Osimertinib seems to be a suitable therapy for treatment-naïve patients with sensitizing and resistant compound  EGFR  mutations. More studies regarding the clinical characteristics of these patients and the appropriate management of this condition are needed to provide the highest standard of care.

An endothelial growth factor receptor compound mutation of T790M substitution with exon 19 deletion in a previously untreated patient: a case report