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.

• Authors: Lei Zhang, Huanhuan Liu, Ye Tian, Huina Wang, Xueying Yang
• Journal: BMC pulmonary medicine (BMC Pulm Med) Vol. 21 Issue 1 Pg. 125 (Apr 17 2021) ISSN: 1471-2466 [Electronic] England
• PMID: 33865348 (Publication Type: Case Reports, Journal Article)

Chemical References

• NCOR2 protein, human
• NTRK1 protein, human
• Nuclear Receptor Co-Repressor 2
• Protein Kinase Inhibitors
• Pyrazoles
• Pyrimidines
• Receptor, trkA
• larotrectinib

Topics

• Adenocarcinoma of Lung (drug therapy, genetics)
• Female
• Humans
• Lung Neoplasms (drug therapy, genetics)
• Middle Aged
• Mutation
• Nuclear Receptor Co-Repressor 2 (genetics, metabolism)
• Protein Kinase Inhibitors (administration & dosage)
• Pyrazoles (administration & dosage)
• Pyrimidines (administration & dosage)
• Receptor, trkA (genetics, metabolism)
• Treatment Outcome