Emergence of NOTCH2-NTRK1 After Osimertinib in a Patient With Lung Adenocarcinoma With Neuroendocrine Differentiation

Abstract

•Osimertinib is widely used in patients with lung cancer with EGFR T790M after EGFR TKI treatment with high efficacy and approved in first-line treatment for all EGFR positive patients. However, the resistance profile to osimertinib is not well-elucidated. NTRK fusions are rare oncogenic drivers in lung cancer. •Here, we report a NOTCH2–NTRK1 rearranged fusion in lung adenocarcinoma with neuroendocrine differentiation after osimertinib treatment. The patient had significantly improved clinical symptoms and had stable disease for 2 months after larotrectinib and osimertinib treatment, with significant decrease in NOTCH2-NTRK1 fusion (AF from 24.85% to 0.63%). •The emergence of NTRK fusions after osimertinib treatment may suggest a therapeutic target. NTRK fusions screening is important after osimertinib resistance. •Osimertinib is widely used in patients with lung cancer with EGFR T790M after EGFR TKI treatment with high efficacy and approved in first-line treatment for all EGFR positive patients. However, the resistance profile to osimertinib is not well-elucidated. NTRK fusions are rare oncogenic drivers in lung cancer. •Here, we report a NOTCH2–NTRK1 rearranged fusion in lung adenocarcinoma with neuroendocrine differentiation after osimertinib treatment. The patient had significantly improved clinical symptoms and had stable disease for 2 months after larotrectinib and osimertinib treatment, with significant decrease in NOTCH2-NTRK1 fusion (AF from 24.85% to 0.63%). •The emergence of NTRK fusions after osimertinib treatment may suggest a therapeutic target. NTRK fusions screening is important after osimertinib resistance.