Table 11.
Common adverse reactions associated with KIs with anti-angiogenic properties. Incidence is from all FDA indications for each KI using the highest percent reported and landmark studies that lead to FDA approval. Percent may be different from smaller phase 2 studies. Grade 2 cardiac dysfunction is defined in CTCAE v4 as symptoms of cardiac dysfunction or ≥ 15% absolute decline in LVEF compared to baseline or a decline in LVEF of ≥ 10% compared to baseline that is also below the lower limit of normal.
| Kinase Inhibitor | Axitinib | Cabozantinib | Pazopanib | Regorafenib | Sunitinib | Sorafenib | Vandetanib |
|---|---|---|---|---|---|---|---|
| No. targets | 1 | 8 | 7 | 14 | 6 | 8 | 7 |
| HTN (all grades) | 40% | 33% | 42% | 30% CRC 59% GIST | 34% | 9% HCC 17% RCC | 33% |
| HTN Grade 3/4 | 16% | 8% | 7% | 8% CRC 28%GI ST | 13% RCC 4% GIST | 4% | 9% |
| Cardiac Dysfunction | EF drop ≥ grade 2; 11% sarcoma | Ischemia 1.2% | EF drop ≥ grade 2; 11% GIST, 27% RCC | Ischemia 2.7% | Few cases | ||
| EF monitor | Patient at risk, i.e., prior doxorubicin | Not required | Patient at risk | ||||
| Hypothyroidism (all grades) | 19%) | N/A | 7% | 4.2% CRC 18% GIST | 4% GIST 16% RCC | Uncommon | N/A |
| Proteinuria (all grades) | 11%) | 2% | 9% | 60% CRC 33% GIST | Few cases | 10% | |
| ALT Elevation | All grade 22% | all grade 86%, grade 3/4 6% | Grade 2≥ 18% | All grade 45% Grade 3/4 6% | All grade 51%, grade 3/4 3% | liver dysfunction 11% not specified as ALT | 51% |
| Pre-surgery | Stop 24 hr before | Stop 28 d before | Stop 7 d before | Stop 14 d before | Physician discretion | Physician discretion | |
| Arterial Thromboembolism | 1∼2% | 2% | 2∼3% | Few cases | Uncommon | Few cases | |
| VTE | 3% | 6% | 5% | 3% | Uncommon | ||
| Any hemorrhage | 13% RCC 22%o Sarcoma | 21% | 37% RCC, 18% GIST | 18% | |||
| Grade 3/4 | 1% | 3% | Grade 4 3% | 2% | 4∼7% | 5% | |
| Hemorrhage | RCC Grade 4 1% Sarcoma | ||||||
| QTc Prolongation | QTc ≥ 500ms; 2% | Rare | 14% | ||||
| Torsades | < 1% | < 0.1% | grade 3/4; 8%, few torsades cases | ||||
| Hand Foot Syndrome (all grades) | 27% | 50% | 6% | 45% CRC 67% GIST | 14% GIST, 29% RCC | 21% HCC, 30% RCC | Few cases |
N/A; Non-applicable due to total thyroidectomy in most patients. Abbreviations: d, day; CTCAE, Common Terminology Criteria for Adverse Events; LVEF, left ventricular ejection fraction, CRC; colorectal cancer, GIST; gastrointestinal stromal tumor.