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.

NTRK Fusion in Non-Small Cell Lung Cancer: Diagnosis, Therapy, and TRK Inhibitor Resistance

“…However, inconsistent result emerged in a case report, where a patient with advanced lung adenocarcinoma harboring a novel NCOR2-NTRK1 fusion showed disease progression after receiving two cycles of anti-PD-1 inhibitor monotherapy, although the presence of high TMB (58.58 mutations/Mb) and positive PD-L1 expression (20%–30% of the tumor cells) was also observed in this case. Predominantly, the patient showed a partial response after switching to TRK inhibitor larotrectinib ( 120 ). It indicates that TRK inhibitor is more effective than anti-PD-1 inhibitor monotherapy for patients with NTRK fusion-positive NSCLC in spite of higher TMB and positive PD-L1 expression simultaneously.…”

Keratin-Positive Giant Cell-Rich Tumor: A Review and Update

“…The NCOR2 gene is widely expressed in human tissues and contains 45 exons [17]. To date, only a small number of NCOR2 fusion partners have been identified, including neurotrophic receptor tyrosine kinase 1 (NTRK1) and GLI family zinc finger 1 (GLI1) [18,19]. Although the oncogenesis of NCOR2 fusions remains unknown, a de-regulating effect on gene expression through interaction with other transcription factors has been suggested [19].…”

Immunotherapy in Non-Small-Cell Lung Cancer Patients with Driver Alterations: A New Strategy?

“…A patient with LUAC, harboring novel NTRK fusion ( NCOR2-NTRK1 ), was treated with camrelizumab (anti-PD-1 mAb) and PD was observed, despite high TMB and PD-L1 positivity (20–30% of tumor cells). However, partial response for at least 5 months was achieved after switching the treatment option to larotrectinib ( Table 2 ) [ 36 ]. Rosen et al performed analysis on patients with TRK fusion, and one patient with LUAC, receiving ICI, achieved stable disease ( Table 2 ) [ 37 ].…”