Coexistence of A Secondary STRN-ALK EML4-ALK Double-Fusion Variant in A Lung Adenocarcinoma Patient withEGFR Mutation: A Case Report

Anaplastic lymphoma kinase (ALK)-positive disease is characterized by the presence of ALK gene rearrangements that encode driver fusion oncoproteins. Echinoderm microtubule-associated protein-like 4 gene (EML4)-ALK fusion is regarded as the most common type and is reported in 2 to 7% of patients with advanced non–small cell lung cancers (NSCLCs). Striatin (STRN)-ALK is a novel ALK fusion partner in NSCLC and is considered sensitive to targeted therapy. However, there was no study regarding effective therapy for EML4-ALK and STRN-ALK double fusion variants in epidermal growth factor receptor (EGFR)-resistant mutant lung cancer. TP53, RB1, and EGFR exon 21 L858R were found in tumor tissues and plasma from patients with capture-based nextgeneration sequencing (NGS). After three months of gefitinib treatment, an NGS of plasma circulating tumor DNA (CTDNA) showed that all variants disappeared significantly, and the tumor mass regressed on computed tomography (CT). However, after 10 months, the patient developed drug resistance and the disease progressed with the appearance of new metastatic lesions in the liver and bones. A repeated NGS test revealed EGFR exon20 T790M and the appearance of a novel double-fusion EML4-ALK and STRNALK. A combined therapeutic regimen of crizotinib plus osimertinib showed a promising prognosis confirmed with lung CT scans showing stable lesion without any new metastasis.