40P Lorlatinib-associated weight gain and dyslipidaemia: A single centre UK experience

Lorlatinib is a third generation ALK inhibitor with marked efficacy in NSCLC. CTCAE-defined weight gain and dyslipidaemia has been reported in patients receiving lorlatinib in registrational trials. Lipid-lowering agents may interact with lorlatinib metabolism. We conducted a single centre retrospective analysis of NSCLC patients receiving lorlatinib. The primary objective was to quantify weight gain and lipid profile changes in accordance with CTCAE v5.0. Extraction from electronic medical records was undertaken by authors. Mean relative dose intensity (RDI) was defined as % of full dose lorlatinib for duration of therapy. All analyses were descriptive. Patients without baseline weight recorded were excluded. The project was approved by the hospital service evaluation committee. 43 patients were evaluable. 77% (n=33/43) were ALK+ and 23% (n=10/43) ROS1+. Mean duration of lorlatinib was 14.5 months. Mean RDI was 81%. Weight gain occurred in 81% (n=35/43) of patients, 44% (n=19/43) Grade≥1 and 9% (n=4/43) Grade≥3. Mean weight gain/BMI was 6.4kg/2.4kg/m2 (range 0-30.1kg/11.4kg/m2). Dietitian referral occurred in 5% (n=2/43). Increase in total cholesterol (TChol) occurred in 51% (n=22/43) and triglyceride in 58% (n=25/43) of patients. 84% (n=36/43) were prescribed statins and 2% (n=1/43) ezetimibe/statin. 35% (n=15/43) patients had normal baseline TChol (20%)4 (9)No8 (19)Unknown1 (2)Cholesterol, n=43 (%)TChol increaseYes22 (51)No21 (49)Mean increase1.94mmol/LMaximum grade of hypercholesterolaemia in pts with normal baseline TChol, n=15 (%)G110 (67)G24 (27)G31 (7)G40 Open table in a new tab Real world prevalence of weight gain was similar to that reported in landmark trials. Dyslipidaemia is frequent and requires active treatment which may impact metabolism of lorlatinib. Larger scale evaluation on quality of life impact and medical risk of weight gain/dyslipidaemia is required.