Table 1.
Pharmacodynamic properties of 15 protein kinase inhibitors and adverse drug reactions contained in VigiBase®
| Drug name (year of approval) | Indications | Main targets |
ICSRs reported in VigiBase® N (%) N = 141 601 |
ICSRs of CF reported in VigiBase® n (%) n = 2594 |
|---|---|---|---|---|
| Afatinib (2013) | Advanced/metastatic NSCLC (EGFR+) | EGFR, HER2, HER3, HER4 | 1442 (1.0) | 15 (0.6) |
| Axitinib (2012) | Advanced RCC | VEGFR‐1, VEGFR‐2, VEGFR‐3 | 3000 (2.1) | 39 (1.5) |
| Bosutinib (2012) | CML (ph+) | Bcr‐abl, CSK, Lyn, Hck, PDGFRs, KIT | 987 (0.7) | 28 (1.1) |
| Crizotinib (2011) | Advanced NSCLC (ALK+) | ALK, MET | 3141 (2.2) | 34 (1.3) |
| Dasatinib (2006) | CML (ph+) | Bcr‐abl, KIT, PDGFRβ, Eph | 9861 (7.0) | 375 (14.5) |
| ALL (ph+) | ||||
| Erlotinib (2004) | Advanced/metastatic NSCLC (EGFR+) | EGFR | 24 891 (17.6) | 240 (9.3) |
| Gefitinib (2003) | Advanced/metastatic NSCLC (EGFR+) | EGFR | 4812 (3.4) | 46 (1.8) |
| Imatinib (2001) | CML (ph+) | Bcr‐abl, KIT, DDR1, DDR2, CSFR, PDGFRα, PDGFRβ | 25 503 (18.0) | 577 (22.2) |
| ALL (ph+) | ||||
| MD/MPD (PDGFR+) | ||||
| HES/CEL (FIP1L1+/PDGFRα+) | ||||
| GIST | ||||
| DFSP | ||||
| Lapatinib (2007) | BC (HER2+) | EGFR, HER2 | 12 030 (8.5) | 164 (6.3) |
| Nilotinib (2007) | CML (ph+) | Bcr‐abl, PDGFRα, PDGFRβ, KIT, EPH | 7589 (5.4) | 175 (6.8) |
| Pazopanib (2009) | Advanced RCC | VEGFR‐1, VEGFR‐2, VEGFR‐3, PDGFRα, PDGFRβ, KIT | 8378 (5.9) | 117 (4.5) |
| Soft‐tissue sarcoma | ||||
| Ruxolitinib (2011) | Myelofibrosis | JAK1, JAK2 | 5513 (3.9) | 79 (3.1) |
| Polycythaemia vera | ||||
| Sorafenib (2005) | Hepatocellular carcinoma | B‐Raf, B‐RafV600E, KIT, FLT3, c‐Raf, VEGFR‐2, VEGFR‐3, PDGFRβ | 15 482 (10.9) | 188 (7.3) |
| Advanced RCC | ||||
| Differentiated thyroid carcinoma | ||||
| Sunitinib (2006) | GIST | PDGFRα, PDGFRβ, VEGFR‐1, VEGFR‐2, VEGFR‐3, KIT, FLT3, Ret, CSFR | 18 303 (12.9) | 508 (19.56) |
| Metastatic RCC | ||||
| Pancreatic neuroendocrine tumours | ||||
| Vandetanib (2011) | Medullary thyroid cancer | VEGFR‐2, EGFR | 669 (0.5) | 9 (0.4) |
| Total | 141 601 (100) | 2594 (100) |
ALK, anaplastic lymphoma receptor tyrosine kinase; ALL, acute lymphoblastic leukaemia; BC, breast cancer; Bcr‐abl, Bcr‐abl fusion protein; B‐Raf, B‐Raf proto‐oncogene, serine/threonine kinase; CEL, chronic eosinophilic leukaemia; CF, cardiac failure; CML, chronic myeloid leukaemia; c‐Raf, Raf‐1 proto‐oncogene, serine/threonine kinase; CSFR, colony‐stimulating factor 1 receptor; CSK, c‐src tyrosine kinase; DDR1, discoidin domain receptor tyrosine kinase 1/2; DFSP, dermofibro sarcoma protuberans; EGFR, epidermal growth factor receptor; EPH, ephrin receptor; FI1L1: FIP1‐like 1 protein; FLT3, receptor‐type tyrosine protein kinase FLT3; GIST, gastrointestinal stromal tumour; Hck, HCK proto‐oncogene, Src family tyrosine kinase; HER2/3/4, erb‐b2 receptor tyrosine kinase 2/3/4; HES, hypereosinophilic syndrome; ICRS, individual case safety report; JAK1/2, tyrosine protein kinase JAK1/2; KIT, KIT proto‐oncogene receptor tyrosine kinase; Lyn: LYN proto‐oncogene, Src family tyrosine kinase; MD/MPD, myelodysplastic/myeloproliferative syndrome; MET, MET proto‐oncogene, receptor tyrosine kinase; NSCLC, nonsmall cell lung cancer; PDGFRα/β, platelet‐derived growth factor receptor alpha/beta; Ph, Philadelphia chromosome; RCC, renal cell carcinoma; Ret, ret proto‐oncogene; VEGFR‐1/2/3, vascular endothelial growth factor 1/2/3