TABLE A3.
Summary of Cardiovascular AEs in Patients With Hyperlipidemia At Baseline and/or Developed During the Study
| Event | Lorlatinib (n = 134) | Crizotinib (n = 32) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Any Gradea | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Any Grade | Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
| Any CV AEs, No. (%) | 37 (28) | 18 (13) | 7 (5) | 8 (6) | 1 (1) | 15 (47) | 8 (25) | 4 (13) | 3 (9) | 0 |
| SMQ ischemic heart disease | 21 (16) | 14 (10) | 1 (1) | 6 (4) | 0 | 10 (31) | 7 (22) | 2 (6) | 1 (3) | 0 |
| Blood creatine phosphokinase increased | 19 (14) | 14 (10) | 1 (1) | 4 (3) | 0 | 10 (31) | 8 (25) | 2 (6) | 0 | 0 |
| Arteriosclerosis coronary artery | 1 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ECG T wave abnormal | 1 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Myocardial infarction | 1 (1) | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Myocardial ischemia | 1 (1) | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Troponin increased | 1 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Blood creatine phosphokinase MB increased | 0 | 0 | 0 | 0 | 0 | 1 (3) | 0 | 0 | 1 (3) | 0 |
| ECG ST segment elevation | 0 | 0 | 0 | 0 | 0 | 1 (3) | 1 (3) | 0 | 0 | 0 |
| ECG T wave inversion | 0 | 0 | 0 | 0 | 0 | 1 (3) | 1 (3) | 0 | 0 | 0 |
| SMQ embolic and thrombotic events, No. (%) | 10 (7) | 3 (2) | 3 (2) | 4 (3) | 0 | 6 (19) | 2 (6) | 2 (6) | 2 (6) | 0 |
| Cerebrovascular accident | 2 (1) | 0 | 0 | 2 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Deep vein thrombosis | 2 (1) | 0 | 2 (1) | 0 | 0 | 1 (3) | 1 (3) | 0 | 0 | 0 |
| Pulmonary embolism | 2 (1) | 2 (1) | 0 | 0 | 0 | 2 (6) | 0 | 2 (6) | 0 | 0 |
| Cerebral ischemia | 1 (1) | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Embolic cerebral infarction | 1 (1) | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Myocardial infarction | 1 (1) | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Sigmoid sinus thrombosis | 1 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cerebral infarction | 0 | 0 | 0 | 0 | 0 | 1 (3) | 0 | 0 | 1 (3) | 0 |
| Thrombophlebitis | 0 | 0 | 0 | 0 | 0 | 1 (3) | 1 (3) | 0 | 0 | 0 |
| Thrombosis | 0 | 0 | 0 | 0 | 0 | 1 (3) | 0 | 0 | 1 (3) | 0 |
| Cluster cardiac failure, No. (%) | 6 (4) | 1 (1) | 2 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Cardiac failure | 2 (1) | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Ejection fraction decreased | 2 (1) | 0 | 1 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Cardiac failure acute | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cardiac failure chronic | 1 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cardiac failure congestive | 1 (1) | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| SMQ hemorrhagic CNS vascular conditions, No. (%) | 4 (3) | 0 | 1 (1) | 1 (1) | 1 (1) | 0 | 0 | 0 | 0 | 0 |
| Cerebrovascular accident | 2 (1) | 0 | 0 | 2 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Basal ganglia hemorrhage | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Subdural hematoma | 1 (1) | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Thalamus hemorrhage | 1 (1) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 |
| SMQ ischemic CNS vascular conditions, No. (%) | 4 (3) | 0 | 1 (1) | 3 (2) | 0 | 1 (3) | 0 | 0 | 1 (3) | 0 |
| Cerebrovascular accident | 2 (1) | 0 | 0 | 2 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Cerebral ischemia | 1 (1) | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Embolic cerebral infarction | 1 (1) | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Cerebral infarction | 0 | 0 | 0 | 0 | 0 | 1 (3) | 0 | 0 | 1 (3) | 0 |
NOTE. Cardiovascular events were cardiac death; sudden cardiac death; sudden death; and SMQ embolic and thrombotic events of cluster cardiac failure, SMQ ischemic heart disease, SMQ ischemic CNS vascular conditions, and SMQ hemorrhagic CNS vascular conditions.
Abbreviations: AE, adverse event; CV, cardiovascular; MedDRA, Medical Dictionary for Regulatory Activities; SMQ, Standardized MedDRA Queries.
a
Three patients in the lorlatinib group died due to cardiac failure, cardiac failure acute, and basal ganglia hemorrhage (n = 1 each).