Table 2.
Cases of Osimertinib-Induced Cardiac Adverse Events
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | |
|---|---|---|---|---|---|---|
| Age, yrs | 78 | 71 | 68 | 64 | 52 | 71 |
| Sex | Female | Female | Male | Female | Female | Female |
| EGFR mutation | L858R | L858R＋T790M | Ex.19 del＋T790M | L858R＋T790M | L858R | L858R |
| Osimertinib line | 2nd | 3rd | 3rd | 3rd | 1st | 1st |
| Osimertinib effect | PR | PR | PR | PR | PR | NE |
| Tobacco | No | No | No | Yes (former) | Yes (former) | No |
| CVD risk/history | HTN Aortic aneurysm |
HTN | Moderate AR HU |
Moderate MR | Obesity | HTN DM |
| Daily medications | Carvedilol 20 mg; Nifedipine CR 40 mg; Azilsartan 40 mg; Rosuvastatin 5 mg |
Amlodipine 5 mg | Allopurinol 100 mg; Prednisolone 5 mg | Prednisolone 7.5 mg | - | Candesartan 8 mg |
| Symptoms | Exertional dyspnea; leg edema |
Fatigue | Leg edema; fatigue |
Facial/leg edema | - | Chest pain; dyspnea |
| Cardiac event | Heart failure; QT prolongation |
MR progression; mitral valve prolapse |
TR progression | EF decline; HTN; MR progression |
EF decline | Acute myocardial infarction |
| CTCAE Grade | 3 | 3 | 3 | 3 | 3 | 4 |
| Time to event | 3 months | 3 months | 1 month | 9 months | 2 weeks | 2 months |
| NT-proBNP or BNP, pg/ml | NT-proBNP 18,890 | BNP 21.9 | NT-proBNP 450 | BNP 227.9 | NT-proBNP 36 | BNP 423.4 |
| LVEF before osimertinib, % | 61 | 82 | 74 | 72 | 63 | 69 |
| LVEF after osimertinib initiation, % | 28 | 74 | 60 | 50 | 41 | 42 |
| CTRCD | Yes | No | No | Yes | Yes | Yes |
| RV biopsy | Yes | No | No | No | Yes | No |
| Valvular disease | MR; (−) → severe (3–4) |
MR; trace (0–1) → severe (3–4), prolapse |
TR; trace (0–1) → moderate–severe (3-4) |
MR; mild–moderate (2–3) → moderate (3) |
- | - |
| Osimertinib treatment | Discontinued | Discontinued | Reduced dosage from 80 mg to 40 mg every other day | Temporarily held and resumed at 80 mg daily | Discontinued | Discontinued |
| Subsequent cancer therapy | Gefitinib | Gefitinib | Osimertinib rechallenge | Osimertinib rechallenge | Afatinib | Erlotinib |
| Treatment for cardiac event (daily medications) | Furosemide 40 mg; Spironolactone 50 mg; Candesartan 2 mg; Carvedilol 5 mg; Tolvaptan 7.5 mg |
Furosemide 20 mg | Furosemide 40 mg; Tolvaptan 3.75 mg |
Furosemide 20 mg; Spironolactone 25 mg | Candesartan 4 mg | PCI for LAD 6 |
| Return of LVEF to baseline | No 48% after 9 months |
Yes 74% after 6 months |
Yes 72% after 2 months |
Yes 62% after 14 months |
Yes 63% after 2 months |
No 54% after 7 months |
AR = aortic valve regurgitation; BNP = brain natriuretic peptide; CTCAE = common terminology criteria of adverse event; CTRCD = cancer therapeutics-related cardiac dysfunction; CVD = cardiovascular disease; DM = diabetes mellitus; LVEF = left ventricular ejection fraction; HTN = hypertension; HU = hyperuricemia; LAD = left anterior descending coronary artery; MR = mitral regurgitation; NA = not available; NE = not evaluable; NT-proBNP = N-terminal pro–B-type natriuretic peptide; PCI = percutaneous coronary intervention; PR = partial response; RV = right ventricle; TR = tricuspid regurgitation.