Background:
Currently, many targeted drugs are approved for treatment of ALK fusion non-small cell lung cancer. However, it has been previously assumed that patients with 5' non-oncogenic kinase (5' NOK) fusion detected by DNA next-generation sequencing (NGS) would not benefit from ALK inhibitors because of lack of an intact kinase domain.
Case description:
A novel 5' NOK fusion form, ALK-CYP27C1 (A19:C5), was detected by DNA NGS in surgical tissue specimens of a patient with recurrent lung adenosquamous carcinoma. The patient achieved 29 months of progression-free survival with ensartinib treatment. The results of RNA NGS from the same operative tissue identified EML4-ALK (E13:A20) fusion variant type I.
Conclusion:
This is the first case to provide real-world evidence of effective treatment of a patient with the 5' NOK fusion form at the DNA level but functional EML4-ALK at the RNA level, illustrating the need for RNA testing in 5' NOK patients.