Severe lorlatinib-induced dyslipidaemia successfully managed with a PCSK9 inhibitor in a patient with ALK-positive non-small cell lung cancer: A case report

Background: Advances in cancer therapy have substantially improved survival in patients with malignant disease, but they have also revealed new long-term complications, including cardiovascular and metabolic adverse effects. Dyslipidaemia is a clinically important complication of several anticancer therapies. It is particularly frequent and pronounced during treatment with lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) inhibitor used in ALK-positive non-small cell lung cancer (NSCLC). Case presentation: We report the case of a 75-year-old woman with advanced ALK-positive NSCLC who was initially treated with alectinib, which was discontinued because of hepatotoxicity. After initiation of lorlatinib, the patient developed severe dyslipidaemia within 8 days, with total cholesterol increasing to 20.3 mmol/L and triglycerides to 42 mmol/L. Combination lipid-lowering therapy with rosuvastatin, fenofibrate and later ezetimibe led to partial stabilisation of the lipid profile. In June 2025, evolocumab was added, resulting in a 70% reduction in total cholesterol and an approximately 76% reduction in triglycerides. This allowed continuation of effective anticancer therapy. The patient has remained clinically stable for more than 5 years without progression of the oncological disease. Conclusion: Lorlatinib-induced dyslipidaemia may be severe, rapid in onset and clinically challenging. Early lipid monitoring, prompt lipid-lowering treatment and multidisciplinary cooperation between oncologists, internists, cardiologists and lipid specialists are essential. In selected patients with refractory dyslipidaemia, PCSK9 inhibitors may represent an effective therapeutic option that enables continuation of life-prolonging oncological treatment.