Case Report: Treatment Response of SQSTM1 -ALK Fusion Lung Adenocarcinoma Treated with Multiple ALK Inhibitors

Jincui Gu^*Jing ZhangShaoli LiZiying LinLixia Huang^*Yanbin Zhou^*

• The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China

The echinoderm microtubule-associated protein-like 4 gene (EML4) and anaplastic lymphoma kinase (ALK) gene fusion is the most common ALK rearrangement in non-small cell lung cancer (NSCLC). In 2015, SQSTM1 (exon5)--ALK (exon 20) in patients with NSCLC was found. However, the treatment of lung adenocarcinoma patients with SQSTM1-ALK fusion has not been reported. Here, we report for the first time an SQSTM1-ALK fusion in a stage IV lung adenocarcinoma patient who had a variable response after sequential treatment with alectinib, ensartinib, lorlatinib and brigatinib, successively.The biopsy specimen was subjected to hematoxylin-eosin (HE) staining, immunohistochemistry (IHC) and next-generation sequencing (NGS).The patient responded to alectinib as a first-line treatment and achieved stable disease for 16 months, without significant symptoms of toxicity. Ensartinib may have a better effect on brain metastases. As third-line therapy, lorlatinib has a PFS of 15 months. And as fourth-line therapy, brigatinib only has a PFS of 2 months.This is the first report of a patient with SQSTM1-ALK fusion who had different responses after treatment with alectinib, ensartinib, lorlatinib and brigatinib. We hope that our case may provide clinical evidence for the treatment strategy of this rare variant and further supporting the individualized application of ALK-TKIs in patients with non-classical fusions.