Replacement of ALK inhibitors as an effective strategy for reducing drug toxicity in non-small cell lung cancer patients with ALK gene rearrangement

This case report examines the effects of replacement of anaplastic lymphoma kinase inhibitor (ALKi) as a strategy to reduce drug toxicity in patients with non-small cell lung cancer (NSCLC) with ALK gene rearrangements. A 61-year-old female patient with lung adenocarcinoma encountered difficulties in ALK abnormalities diagnosis: the expression of abnormal ALK protein was not detected by the immunohistochemistry (IHC) assay, but ALK gene rearrangement was present in next generation sequencing (NGS) and fluorescence in situ hybridization (FISH) assays. The patient was initially treated with second-generation ALKi (alectinib). However, the patient experienced severe hepatotoxicity. She was successfully switched to brigatinib (another second-generation ALK inhibitor). During brigatinib therapy, a transient increase in creatinine kinase concentration was observed, which required brigatinib dose reduction. Effectiveness of both anti-ALK agents was observed (partial response to treatment, followed by disease stabilization). This case report illustrates the difficulties in diagnosing ALK gene rearrangements and the possibility of replacing ALK inhibitors without compromising treatment efficacy.