A real-world analysis of dyslipidemia and attributable risk in lorlatinib-treated ALK-positive lung cancer patients.

Abstract

e24190 Background: Lorlatinib as a first-line treatment for ALK-positive NSCLC can significantly prolong survival, and the most common adverse reaction is hyperlipidemia, and relevant management data are lacking. This study aims to identify risk factors for poor lipid control in the real world and provide an evidence-based basis for clinical management. Methods: This study retrospectively analyzed patients with stage III-IV ALK-positive advanced NSCLC who received lorlatinib treatment across multiple centers between May 1, 2022, and April 30, 2025. Data on patient baseline characteristics, blood lipid levels (TG,TC,LDL-C) before and after treatment, and lipid-lowering medication use were collected, with further attributable risk analysis of factors associated with poor lipid control. Results: This study enrolled a total of 306 patients from 12 participating centers. Baseline characteristics are detailed in Table 1. Within 9 months of treatment, patients receiving lorlatinib exhibited a marked abnormal elevation in lipid levels (Figure 1), with no significant improvement observed through the 36-week follow-up endpoint, regardless of lipid-lowering medication use (Figure 2). These findings indicate that conventional lipid-lowering interventions fail to effectively ameliorate lorlatinib-associated hyperlipidemia, highlighting an urgent need to optimize clinical management strategies for this drug-induced dyslipidemia. Poor medication adherence was the strongest risk factor, with a Population Attributable Risk Percentage (PAR%) of 26.5%, Attributable Risk Percentage (ARP) of 37.3%, and a population exposure rate of 60.5%. Lack of regular follow-up (patient non-compliance) was the second strongest risk factor (PAR% of 9.2%), with a 100% poor lipid control rate among patients who did not attend follow-up visits. The protective effect of smoking history requires further validation with a larger sample size. Conclusions: This study indicates that poor adherence to lipid-lowering medications and lack of regular follow-up are the most important modifiable risk factors for poor control of hyperlipidemia in lung cancer patients treated with lorlatinib. Addressing these factors may significantly improve lipid management in this population. Patient characteristics. Characteristics Sex Male 144（47.05%） Female 162（52.95%） Age <65 234（76.5%） ≥65 72（23.5%） Smoke Yes 53（17.3%） No 253（82.7%） ECOG 0-1 237（77.5%） ≥2 69（22.%） Health History Diabetes 53（17.3%） Hypertension 40（13.1%） Hyperlipidemia 35（11.4%） Lipid-Lowering Drugs Yes 41（13.4%） No 265（86.6%） Histology Adenocarcinoma 4（1.3%） Squamous cell carcinoma 287（93.8%） Other 15（4.9%） TNM Staging III 19（6.2%） IV 287（93.8%） Treatment Lines 1line 141（46.%） 2line 62（20.3%） 3line 37（12.1%） ≧3line 66（21.6%）