Table 1.
Small molecule tyrosine kinase inhibitors (modified from Current Oncology Reports, Tyrosine Kinase Inhibitors and Vascular Toxicity: Impetus for a Classification System?, volume 18, issue 6, page 33, year 2016, Joerg Herrmann, with permission of Springer).
| Malignancy targets | Molecular Targets | HTN | Chest pain | MI | Stroke/TIA | PAD | DVT/PE | Additional warnings | |
|---|---|---|---|---|---|---|---|---|---|
| Bcr/Abl inhibitors | |||||||||
| Imatinib | Ph+ CML, Ph+ ALL, GIST, ASM, MDS Off-label melanoma | ABL-1, c-KIT, PDGFR-A, PDGFR-B, FLT-3 | 4% | 7–11% | Edema 11–86% Hypotension 11% | ||||
| Nilotinib | Ph+ CML Off-label GIST | ABL-1, c-KIT, PDGFR-A, PDGFR-B, FLT-3 | 10–11% | 5–9% | 1–3% | 3–4% | Pericardial effusion 2% | ||
| Ponatinib | Ph+ CML, Ph+ ALL | ABL-1, c-KIT, PDGFR-A, PDGFR-B, FLT-1, KDR, FLT-3, FLT-4, FGFR, SRC, TIE2 | 53–71% | 12% | 2% | 8% | 5% | HF6–15% Pericardial effusion 1–3% Atrial fibrillation 4% | |
| Bosutinib | Ph+ CML | ABL-1, FGFR, FLT-1, FLT-2, FLT-3, KDR, PDGFR-A, PDGFR-B, SRC | Edema 14% Pericardial effusion 1–3% | ||||||
| Dasatinib | Ph+ CML, Ph+ ALL Off-label GIST | ABL-1, FGFR2, KIT, PDGFR-A, PDGFR-B, SRC | 4% IHD | Edema 4% Pericardial effusion 4% Cardiac dysfunction 4% QTc prolongation 1% Conduction abnormalities 7% | |||||
| VEGFR inhibitors | |||||||||
| Sorafenib | RCC, Thyroid cancer, HCC, off-label: angiosarcoma and GIST | B-Raf, FLT-1, FLT-3, FLT-4, KDR, KIT, PDGFR-A, PDGFR-B, FGFR, c-fms | 9–41% (grade 3 or 4 10%) | 3% | 1% | HF in 2% | |||
| Sunitinib | RCC, GIST, PNET, off-label: STS, thyroid cancer | ABL-1, c-KIT, PDGFR-A, PDGFR-B, FLT-1, KDR, FLT-3, FLT-4, FGFR, SRC, c-smc | 27–34% (grade 3 or 4 10%) | 13% | 3% each | LVEF drop 16–27% | |||
| Pazopanib | RCC, STS, thyroid cancer | ABL-1, c-KIT, PDGFR-A, PDGFR-B, FLT-1, KDR, FLT-4, FGFR, c-frns | 40% (grade 3 or 4 7%) | 5–10% | 2% | 1% | 1–5% | HF 11% QTc prolongation 2% Bradycardia 2–19% | |
| Axitinib | RCC | c-KIT, PDGFR-A, PDGFR-B, FLT-1, KDR, FLT-4, | 40% (grade 3 or 4 16%) | 2% | 1% | 1–3% | |||
| Regorafenib | GIST, colorectal cancer | PDGFR-B, FLT-1, KDR, FLT-4, TIE2, RET, c-KIT, RAF | 30–59% (grade 3 or 4 8–28%) | 1% | |||||
| Lenvatinib | Thyroid cancer | PDGFR-B, FLT-1, KDR, FLT-4, RET, c-KIT | 73% (grade 3 or 4 44%) | 3% | LVEF drop 2% QTc prolongation 9% | ||||
| EGFR inhibitors | |||||||||
| Erlotinib (+gemcitabine) | NSCLC, pancreatic cancer | EGFR (HER1) | N/a | 12% | (2%) | (3%) | N/a | (4%) | (Cardiac arrhythmia 5%, syncope 5%, thrombosis 11%) |
| Vandetanib | Thyroid cancer | EGFR, KDR, FLT-4, RET | 33% (grade 3 or 4–9%) | 1% | QTc prolongation 14% Heart failure 2% | ||||
| ALK inhibitors | |||||||||
| Crizotinib | NSCLC | ALK,MET, ROS1 | 6% | QTc prolongation 5–6% Bradycardia 5–15% Syncope 1–3% Edema 31–49% | |||||
| Ceritinib | NSCLC | ALK, IGF-1R, ROS1, InsR | QTc prolongation 4% Bradycardia 3% | ||||||
| JAK inhibitors | |||||||||
| Ruxolitinib | Myelofibrosis Polycythemia vera | JAK1, JAK2, TYK2 | 6% |