Abstract
Clinical Practice Points • 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.
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