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Gregory J. Riely, MD, PhD


Use of Entrectinib in Lung Adenocarcinoma Harboring EML4::NTRK3 Gene Fusion: Case Report

By: Joshua D. Madera, MS
Posted: Friday, December 23, 2022

Although rare, the genetic fusion of EML4::NTRK3 may serve as a therapeutic target for some patients with non–small cell lung cancer (NSCLC), according to a case report published in Frontiers in Oncology. Use of the NTRK inhibitor entrectinib showed activity in a patient with stage IV lung adenocarcinoma with the aforementioned gene fusion, explained Maria Giulia Cangi, MD, of the IRCCS San Raffaele Scientific Institute, Milan, Italy, and colleagues.

The patient was a 45-year-old female never-smoker with stage IV lung adenocarcinoma who had pleural, bilateral lesions. There was involvement of the mediastinal lymph nodes, right pubic symphysis, and sternum. An MRI showed multiple metastases to the thoracic spinal cord and the subtentorial and supratentorial brain sites. Identification of involved genes was determined using targeted next-generation sequencing analysis. This revealed the EML4::NTRK3 gene fusion, which was further confirmed with both immunohistochemistry staining and fluorescence in situ hybridization.

The patient was subsequently started on treatment with entrectinib. After 2 months of treatment, PET and MRI showed a partial response, which led to the decision to continue the patient’s treatment regimen. The most recent imaging performed revealed a complete radiologic regression of her disease.

“These findings have opened new questions, whether [to] withhold brain radiation in patients with brain lesions carrying targetable alterations amenable to inhibition with agents that penetrate the blood-brain barrier and result in significant control of brain disease,” stated Dr. Cangi and colleagues.

Disclosure: The study authors reported no conflicts of interest.

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