ETV6-NTRK2 fusion in a patient with metastatic pulmonary atypical carcinoid successfully treated with entrectinib: A case report and review of the literature

Background Pulmonary atypical carcinoid (AC) is an extremely rare neuroendocrine tumor. The neurotrophic tropomyosin receptor kinase (NTRK) fusions are reported in only 0.5% of non-small cell lung cancer (NSCLC), and are more rare in AC with only one previously reported case. Currently, there is little established evidence on the optimal therapeutic strategies and prognosis for advanced cases. Case Description We present a female patient with metastatic AC after complete resection. Due to low expression of somatostatin receptor (SSTR) in this case, somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) were not available. After pursuing other alternative treatments, including chemotherapy (i.e. carboplatin, etoposide, capecitabine, temozolomide and paclitaxel), everolimus and atezolizumab, she returned with significant progression, including innumerable subcutaneous nodules, left pleura metastasis, multiple bone metastases, and brain metastases. New biopsy analysis revealed an ETV6-NTRK2 fusion. She was immediately administered the first-generation TRK inhibitor entrectinib at a dose of 600 mg q.d. A subsequent month of treatment resulted in a complete response in all of the metastatic lung lesions. To date, she has maintained sustained benefit for at least one year from initiation of entrectinib. Conclusion Here, we present the first case of a female patient with metastatic AC harboring the ETV6-NTRK2 fusion, and successfully treated with entrectinib, providing evidence for the application of entrectinib in patients with NTRK-positive AC, and underscoring the critical role of molecular profiling for such cases.