Classical ALK G1202R resistance mutation was identified in a lung adenocarcinoma patient with rare LOC388942-ALK fusion after sequential treatment with ALK-TKIs and anlotinib: a case report

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) is a heterogeneous disease. To date, more than ninety ALK fusions in lung cancer have been found. Here, we report for the first time a rare LOC388942-ALK fusion in NSCLC was sensitive to crizotinib but resistant to the sequential ceritinib and alectinib and acquired classical ALK G1202R resistance mutation after long-term treatment with anlotinib. This case highlights dynamic monitoring of gene alteration using next-generation sequencing (NGS) is necessary during the anti-tumor process. CASE DESCRIPTION: A 55-year-old male, with no history of smoking history and no family history of cancer, was found malignant pleural effusion and multiple metastasis nodules in the left lung. He was histopathologically diagnosed with ALK-positive cT4N0M1a adenocarcinoma in June 2016. NGS of the tumor identified a rare LOC388942-ALK fusion (L intergenic: A 20, 1.41%). Then, the patient was treated with chemotherapy, crizotinib, ceritinib, alectinib, and anlotinib sequentially. The patient achieved partial response (PR) to chemotherapy and crizotinib. No evidence of a secondary resistant molecular event was found after resistance to crizotinib, ceritinib, or Alectinib. After 8 months of alectinib treatment, the tumor gradually enlarged again. Anlotinib was followed for 13 months. Thirteen months later, new lesions in the lower lobe of the right lung appeared and increased gradually, indicating definite progression of the tumor. Classical ALK G1202R resistance mutations was detected using cfDNA NGS. The patient refused to receive lorlatinib targeting G1202R resistance mutations and continued with anlotinib. He dead in August 2022, achieving 5-year overall survival (OS). CONCLUSIONS: Distinct ALK fusions in NSCLC have different cancer biology, leading to different response to ALK tyrosine kinase inhibitors (ALK-TKIs), even developed different resistance mechanism. Reporting the clinical details of rare ALK fusions in NSCLC is necessary to guide the treatment for clinicians and researchers.