A novel NCOR2-NTRK1 fusion detected in a patient of lung adenocarcinoma and response to larotrectinib: a case report

Abstract

Background: The identification of NTRK fusions in tumours has become critically important due to the actionable events predictive of response to TRK inhibitor. It is not clear whether the NTRK breakpoint location is different for response to targeted therapy and NTRK fusions affects the efficacy of immunotherapy.

Case presentation: Here we reported a 60-year-old female diagnosed with advanced lung adenocarcinoma. NGS-based molecular profiling identified a novel NCOR2-NTRK1 fusion and high tumor mutational burden (TMB) (58.58 mutations/Mb) in this case. Additionally, program death-ligand 1 (PD-L1) expression was detected in 20-30% of the tumor cells by immunohistochemical (IHC) staining. The patient received treatment with anti-PD-1 immune checkpoint inhibitor of camrelizumab. After two cycles of treatment, the CT scan showed some tumor nodules were still enlarged, indicating disease progression. She was then changed to TRK inhibitor larotrectinib. One month later, the CT scan showed the volume of some lesions started to decrease, and no metastasis lesions were found. The patient then continued the administration of larotrectinib, and some lesion sizes were significantly reduced or even disappeared in the next few months. Currently, this patient is still alive.

Conclusions: Altogether, this report provided a new driver of lung adenocarcinoma expanded the mutational spectrum of NTRK1 fusion variants and suggested using larotrectinib as the targeted therapy is more effective than anti-PD-1 inhibitor in lung adenocarcinoma harboring with NTRK fusion, positive PD-L1 expression, and high TMB simultaneously.

Keywords: Case report; Larotrectinib; Lung adenocarcinoma; NTRK fusion; PD-L1.

Fig. 1

The chest computed tomography (CT) scan images showing the locations of tumor lesions found in a left pleural effusion of lung when the patient presented with dyspnea in June 2019; b after thoracentesis, two metastatic nodules in the left lower lobe; c after accepted PD-1 inhibitor Camrelizumab, 200 mg/time, twice per week, for a total of 4 injections (2 cycles), the tumor nodules were still increased, indicating the disease progressed; d After taking larotectinib, 200 mg/day, orally for 1 month, some lesions showed decreased in size; e oral administration of larotectinib for 3 months indicated some cancerous lesions were continuously reduced in size; f Oral administration of larotectinib for 6 months showed that some cancerous lesions either are reducing or even disappeared

Fig. 2

Immunohistochemical (IHC) analysis showed PD-L1 was expressed in 20–30% of lung tumor cells of this patient (a, b) as compared with the positive control (c). The antibody of PD-L1 (VentanaSP263) was purchased from Roche, San Francisco, CA, USA)

Fig. 3

Next-generation sequencing findings for the tumor tissue sample. a A novel intergenic region between NCOR2 and NTRK1 fusion variant was identified, and b next-generation sequencing results showing break point of NCOR2-NTRK1 fusion