Anaplastic lymphoma kinase (ALK) rearrangements are rare but highly actionable drivers in non-small cell lung cancer; however, uncommon fusion variants lack standard management. We report the clinical outcome of a novel HEAT repeat protein 5B (HEATR5B)-ALK fusion treated with ensartinib. A 52-year-old Chinese woman with stage IVA lung adenocarcinoma and left adrenal metastasis underwent tumor biopsy. Targeted DNA-based next-generation sequencing (NGS) identified HEATR5B(END..EX7)-ALK(IVS19..END) fusion; ALK protein expression was confirmed by immunohistochemistry (IHC). Ensartinib 225 mg orally once daily was initiated. Serial CT scans were evaluated according to RECIST 1.1; progression-free survival (PFS) and adverse events were recorded. The patient achieved a confirmed partial response at first restaging and maintained treatment for greater than 24 months without radiologic progression. No grade greater than or equal to 3 adverse events were observed; preexisting weight loss ceased. PFS is ongoing at the last follow-up (24+ months). The HEATR5B-ALK fusion is targetable by ensartinib, producing durable disease control and excellent tolerability. Comprehensive NGS and ALK IHC are essential for detecting rare actionable ALK variants.
Zhang et al. (Tue,) studied this question.