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Acquired Resistance to Entrectinib in Pancreatic Neuroendocrine Tumor: Case Report

By: Celeste L. Dixon
Posted: Thursday, March 2, 2023

In Frontiers in Oncology, two investigators in Taiwan have described what they believe is the first case of a pancreatic neuroendocrine tumor with a rare ETV6::NTRK3 fusion and a coexisting KRAS::K117N mutation, which was confirmed by cell-free DNA analysis. Wen-Chi Wu, PhD, and Ming-Huang Chen, MD, PhD, both of Taipei Veterans General Hospital, reported that a 62-year-old male patient initially responded well to the tyrosine kinase inhibitor entrectinib, a first-generation NTRK inhibitor, after becoming refractory to multiple lines of standard treatment.

However, with the carcinoma at stage IV, the patient later developed resistance to entrectinib. The results of another liquid biopsy demonstrated the emergence of two acquired mutations: NTRK3::G623R and NTRK::G623E. At that point, the KRAS mutation was undetectable.

“Unfortunately, the patient died,” noted the authors, while “waiting for the approval of compassionate use of repotrectinib,” the second-generation TRK inhibitor targeting acquired NTRK fusion mutations. Nevertheless, this case report highlights several important points, wrote Drs. Wu and Chen: the effectiveness of entrectinib in pancreatic neuroendocrine tumor in which the NTRK3 fusion gene is present; the potential role of genomic sequencing after entrectinib failure; the utility of liquid biopsy if there is difficulty in acquiring tissue; and the necessity of further studies regarding NTRK inhibitors in pancreatic neuroendocrine tumors.

Disclosure: The study authors reported no conflicts of interest.

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