Abstract
Anaplastic lymphoma kinase (ALK) fusions have been identified in approximately 5% of non-small cell lung cancer (NSCLC) cases. ALK-tyrosine kinase inhibitors (TKIs) are the standard first-line treatment for patients with ALK-positive (ALK+) advanced NSCLC. Along with widespread use of next-generation sequencing (NGS) for the molecular diagnosis of lung cancer, an increasing number of ALK fusion partners are being reported, with the majority being effective for ALK-TKIs. Here, we present the case of a 42-year-old female with no smoking history who was diagnosed with stage IVB lung adenocarcinoma. Two rare ALK fusions were detected simultaneously by NGS in this patient: latent transforming growth factor beta-binding protein 1 (LTBP1)-ALK and huntingtin-interacting protein 1 (HIP1)-ALK. HIP1-ALK fusion was also detected by further RNA sequencing, but LTBP1-ALK failed to give a positive signal. The patient received alectinib as first-line therapy and consequently achieved a good response. Progression-free survival (PFS) was more than 19 months, and the treatment with alectinib is ongoing currently. During treatment, clinical symptoms disappeared and no significant adverse events occurred. This is the first case report describing a patient with an NSCLC tumor harboring 2 rare ALK fusions who responded to alectinib. Our report enriches the knowledge of ALK fusion sites and provides an effective clinical basis for the screening of sensitive fusions.