Elsevier

Clinical Lung Cancer

Volume 22, Issue 5, September 2021, Pages e712-e715
Clinical Lung Cancer

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

https://doi.org/10.1016/j.cllc.2021.01.015Get rights and content

Clinical Practice Points

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    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.

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    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%).

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    The emergence of NTRK fusions after osimertinib treatment may suggest a therapeutic target. NTRK fusions screening is important after osimertinib resistance.

Introduction

Osimertinib is now the recommended treatment for EGFR T790M-positive lung cancer after prior EGFR TKI treatment.1 And because osimertinib demonstrated efficacy superior to first-generation EGFR tyrosine kinase inhibitor (TKI) in the FLAURA trial, it is now approved as first-line treatment for EGFR mutated patients.2 However, acquired resistance to osimertinib is inevitable and the mechanism is not well-elucidated.3,4 NTRK fusions are oncogenic drivers in many malignant tumors.5 NTRK gene fusions frequency in lung cancer is less than 5%, but a response rate of more than 75% has been reported in patients with NTRK fusions after NTRK fusions inhibitors treatment.6 Here we report a NOTCH2–NTRK1 rearranged fusion in lung adenocarcinoma with neuroendocrine differentiation after osimertinib treatment.

Section snippets

Case Presentation

A 68-year-old woman was admitted to our hospital for a massive right-sided pleural effusion in July 2017. Positron emission tomography–computed tomography examination after drainage revealed pulmonary mass in the right upper lung and multiple metastatic lesions in the lungs, the right pleura, and the bones. Ultrasound-guided percutaneous lung biopsy revealed a pathologic diagnosis of lung adenocarcinoma with neuroendocrine differentiation (Figure 1). Subsequent targeted next-generation

Discussion

Our case report describes a NOTCH2-NTRK1 rearranged fusion after osimertinib treatment in lung adenocarcinoma with neuroendocrine differentiation. So far, this case report is the first for the emergence of NOTCH2-NTRK1 rearranged fusion after osimertinib treatment.

The prevalence of NTRK1 fusions is extremely rare in lung cancer.7 Xia et al8 reported NTRK1 fusions accounted for only 0.073% (10 in 21115 cases) of all lung adenocarcinoma in a large-scale survey in a Chinese patients with lung

Conclusions

Our case suggests that NOTCH2–NTRK1 could be another possible target of osimertinib resistance. Further research is needed to elucidate the mechanism.

Disclosure

The authors declare no conflict of interest.

Acknowledgments

The authors thank the patient and her family for giving consent in this study.

References (17)

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Cited by (3)

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G. Lin, Y. Liu, and H. Li contributed equally to this work.

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