TABLE A2.
Summary of All-Causality Cardiovascular AEs
| Event | Lorlatinib (n = 149) | Crizotinib (n = 142) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Any Gradea | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Any Grade | Grade 1 | Grade 2 | Grade 3 | Grade 4 | |
| Any AEs, No. (%) | 42 (28) | 19 (13) | 8 (5) | 10 (7) | 1 (1) | 40 (28) | 15 (11) | 13 (9) | 11 (8) | 1 (1) |
| SMQ ischemic heart disease, No. (%) | 21 (14) | 14 (9) | 1 (1) | 6 (4) | 0 | 25 (18) | 15 (11) | 3 (2) | 6 (4) | 1 (1) |
| Blood creatine phosphokinase increased | 19 (13) | 14 (9) | 1 (1) | 4 (3) | 0 | 25 (18) | 16 (11) | 3 (2) | 5 (4) | 1 (1) |
| 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 | 2 (1) | 1 (1) | 0 | 1 (1) | 0 |
| ECG ST segment elevation | 0 | 0 | 0 | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 | 0 |
| ECG T wave inversion | 0 | 0 | 0 | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 | 0 |
| SMQ embolic and thrombotic events, No. (%) | 13 (9) | 4 (3) | 4 (3) | 4 (3) | 0 | 16 (11) | 3 (2) | 8 (6) | 5 (4) | 0 |
| Deep vein thrombosis | 3 (2) | 1 (1) | 2 (1) | 0 | 0 | 6 (4) | 2 (1) | 4 (3) | 0 | 0 |
| Pulmonary embolism | 3 (2) | 2 (1) | 0 | 0 | 0 | 5 (4) | 0 | 3 (2) | 2 (1) | 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 |
| Monoparesis | 1 (1) | 0 | 1 (1) | 0 | 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 (1) | 0 | 0 | 1 (1) | 0 |
| Ischemic stroke | 0 | 0 | 0 | 0 | 0 | 1 (1) | 0 | 0 | 1 (1) | 0 |
| Retinal vein occlusion | 0 | 0 | 0 | 0 | 0 | 1 (1) | 0 | 1 (1) | 0 | 0 |
| Superior vena cava syndrome | 0 | 0 | 0 | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 | 0 |
| Thrombophlebitis | 0 | 0 | 0 | 0 | 0 | 1 (1) | 1 (1) | 0 | 0 | 0 |
| Thrombosis | 0 | 0 | 0 | 0 | 0 | 1 (1) | 0 | 0 | 1 (1) | 0 |
| Cluster cardiac failure, No. (%) | 7 (5) | 1 (1) | 2 (1) | 2 (1) | 0 | 1 (1) | 0 | 1 (1) | 0 | 0 |
| Cardiac failure | 3 (2) | 0 | 1 (1) | 1 (1) | 0 | 1 (1) | 0 | 1 (1) | 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 ischemic CNS vascular conditions, No. (%) | 5 (3) | 0 | 1 (1) | 4 (3) | 0 | 2 (1) | 0 | 0 | 2 (1) | 0 |
| Cerebrovascular accident | 2 (1) | 0 | 0 | 2 (1) | 0 | 0 | 0 | 0 | 0 | 0 |
| Carotid artery disease | 1 (1) | 0 | 0 | 1 (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 (1) | 0 | 0 | 1 (1) | 0 |
| Ischemic stroke | 0 | 0 | 0 | 0 | 0 | 1 (1) | 0 | 0 | 1 (1) | 0 |
| SMQ hemorrhagic CNS vascular conditions, No. (%) | 4 (3) | 0 | 1 (1) | 1 (1) | 1 (1) | 1 (1) | 0 | 1 (1) | 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 | 1 (1) | 0 | 1 (1) | 0 | 0 |
| Thalamus hemorrhage | 1 (1) | 0 | 0 | 0 | 1 (1) | 0 | 0 | 0 | 0 | 0 |
NOTE. Cardiovascular events were cardiac death; sudden cardiac death; sudden death; and the 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; MedDRA, Medical Dictionary for Regulatory Activities; SMQ, Standardized MedDRA Queries.
a
Four patients in the lorlatinib group died due to pulmonary embolism, cardiac failure, cardiac failure acute, and basal ganglia hemorrhage (n = 1 each).