Three lines of treatment with ALK inhibitors in a patient with adenocarcinoma of the lung with ALK gene rearrangement

Lung adenocarcinoma (ADC) with anaplastic lymphoma kinase ( ALK ) gene rearrangement poses treatment challenges due to its aggressive nature and propensity for central nervous system (CNS) metastasis. This report is the case of a 61-year-old male patient with ALK rearranged ADC who underwent three lines of ALK inhibitor (ALKi) therapy: crizotinib, alectinib, and lorlatinib. The patient's initial treatment with a first-generation ALKi — crizotinib (24 months) — was discontinued due to progression of the primary lesion and CNS metastases, resulting in a switch to alectinib (a second-generation ALKi). However, elevated serum total bilirubin levels during therapy necessitated a reduction in the dose of alectinib. While complete regression of CNS lesions was initially achieved, further disease progression occurred after 11 months of alectinib treatment. Subsequent treatment with lorlatinib, a third-generation ALKi, resulted in stabilization of lung lesions and CNS oligoprogression . The dose was reduced due to the patient's anxiety disorder and elevated total cholesterol and triglyceride levels. Ongoing therapy is showing satisfactory results. This case report highlights the importance of individualized treatment strategies based on toxicity profiles and clinical responses in ALK -positive lung ADC with CNS metastases.