Case Report: Long-term survival of a patient with lung adenocarcinoma harboring EGFR 19del/T790M/C797S and KIF26B-NTRK1 rearrangement

Epidermal growth factor receptor (EGFR) gene mutation stands as one of the most prevalent driver genetic alterations in non-small cell lung cancer (NSCLC). While targeted therapies against EGFR have substantially enhanced patient prognosis, acquired resistance remains a core challenge that limits therapeutic efficacy. Patients with stage IV NSCLC generally exhibit a dismal prognosis, with only about 7% of those with stage IVB disease surviving beyond five years. Herein, we report a case of a 47-year-old female patient diagnosed with advanced lung adenocarcinoma, whose clinical course has persisted for nearly a decade. Initial genetic testing identified an EGFR exon 19 deletion (19del). Following treatment with osimertinib, the patient developed concurrent cis-arranged EGFR T790M/C797S double mutations and a neurotrophic receptor tyrosine kinase 1 (NTRK1) gene rearrangement. Subsequently, through a multimodal therapeutic strategy integrating local intervention, radiation therapy, and targeted therapy, the patient’s disease has been sustainably controlled for several years, and she remains alive with stable clinical status to date. NTRK1 fusions are a well-defined mechanism of acquired resistance to EGFR-TKIs, but they are uncommon. This case reports a KIF26B-NTRK1 rearrangement not previously described in lung cancer; however, its functional significance remains to be confirmed. The principal value of this report lies in the completeness of the longitudinal molecular and clinical record, which documents how an on-target mutation and a bypass rearrangement can coexist and persist.