Table 5.
Advances of VEGFR-associated multi-targeted TKIs
| Drug | Brand name | Manufacturer | Targets | Applications of diseases | Approved years or current phases of clinical trials |
|---|---|---|---|---|---|
| Sorafenib | Nexavar | Bayer | VEGFR1-3, TIE2, PDGFR, FGFR, BRAF, CRAF, KIT, FLT-3 | mRCC | 2005 [203] |
| Unresectable HCC | 2007 [109, 110] | ||||
| metastatic DTC | 2013 [204] | ||||
| Sunitinib | Sutent | Pfizer Inc | VEGFR-1–2, PDGFR, FLT3, KIT | GIST after disease progression on or intolerance to imatinib | 2006 [172] |
| mRCC | 2006 [172] | ||||
| unresectable or metastatic pancreatic neuroendocrine tumor | 2011 [205] | ||||
| Adjuvant treatment for RCC | 2017 | ||||
| Vandetanib | Caprelsa | AstraZeneca | EGFR, VEGFR2-3, RET | Unresectable or metastatic MTC | 2011 [206] |
| Regorafenib | Stivarga | Bayer | VEGFR1-3, TIE2, PDGFR, FGFR, BRAF, KIT, RET | Recurrent or metastatic CRC, locally advanced/unresectable or metastatic GIST previously treated with imatinib and sunitinib, advanced HCC who has been previously treated with sorafenib | 2012 [207] , 2013 [173], 2017 [114] |
| Lenvatinib | Lenvima | Eisai Inc | VEGFR1-3, PDGFR, FGFR 1–4, RET, KIT | Radioactive iodine refractory DTC | 2015 [208] |
| 2L combined with everolimus for mRCC | 2016 [209] | ||||
| 1L unresectable HCC | 2018 [111] | ||||
| Combined with pembrolizumab for certain types of endometrial cancer | 2019 [210] | ||||
| Cabozantinib | Cometriq/Cabometyx | Exelixis Inc | VEGFR1-3, MET, ROS1, RET, AXL, NTRK, KIT | Progressive metastatic MTC | 2012 [211] |
| 2L mRCC | 2016 [212] | ||||
| 1L mRCC | 2017 | ||||
| HCC who has been previously treated with sorafenib | 2019 [115] | ||||
| Axitinib | Inlyta | Pfizer Inc | VEGFR1-3, PDGFR, KIT, FLT-3 | 2L advanced RCC | 2012 [213] |
| 1L combined with pembrolizumab for advanced RCC | 2019 [214] | ||||
| 1L combined with avalumab for advanced RCC | 2019 [215] | ||||
| Pazopanib | Votrient | GlaxoSmithKline | VEGFR, PDGFR, KIT | Advanced RCC | 2009 |
| Advanced STS who has previously received chemotherapy | 2012 | ||||
| Anlotinib | - | Jiangsu ChiaTai Tianqing | VEGFR2-3, FGFR1-4, PDGFR, KIT, RET | ≥ 3L metastatic NSCLC | 2018& [117] |
| ≥ 2L metastatic STS | 2018& [216] | ||||
| ≥ 3L relapsed SCLC | 2019& [118] | ||||
| Many other solid tumors | ongoing | ||||
| Fruquintinib | - | Chi-Med | VEGFR1-3 | ≥ 3L mCRC | 2018& [217] |
| Apatinib | - | Jiangsu Hengrui | VEGFR2, KIT, RET, c-Src | ≥3L adenocarcinoma of the stomach or gastroesophageal junction | 2014& [218] |
| 2L HCC | 2020& Applying for approval [116] | ||||
| Investigational drugs | |||||
| Surufatinib | - | Chi-Med | VEGFR1-3, FGFR, CSF-1R | 1L non-pancreatic NET | 2019& Received a NDA [219] |
| Pancreatic NET, solid tumors, biliary tract cancer | I-III ongoing | ||||
| Famitinib | - | Jiangsu Hengrui | VEGFR2-3, PDGFR, FLT1, FLT3, KIT | CRC, NSCLC | III ongoing |
| Multiple solid tumors | I-II ongoing | ||||
| Donafenib | - | Suzhou Zelgen | VEGFR, PDGFR | HCC, CRC, DTC, NPC | I-III ongoing |
| Cediranib | - | AstraZeneca | VEGFR1-3, KIT, PDGFR | Combined with olaparib for ≥ 2L SCLC | II [220] |
In the last column of “Approval years or current phases of clinical trials”, if a drug has been approved, we provided data of the year of its approval by Food and Drug Administration (FDA), except those with a superscript “&” which means they were firstly approved by National Medical Products Administration (NMPA); if a drug is under investigation, we provided current phases of its clinical trials
NSCLC non-small cell lung cancer, SCLC small cell lung cancer, mRCC metastatic renal cell carcinoma, HCC hepatocellular carcinoma, DTC differentiated thyroid cancer, MTC medullary thyroid cancer, CRC colorectal cancer, GIST gastrointestinal stromal tumor, STS soft tissue sarcoma, NPC nasopharyngeal carcinoma, NET neuroendocrine tumors, FLT3 fetal liver tyrosine kinase receptor 3, NDA new drug application, VEGFR vascular endothelial growth factor receptor
Data source: www.fda.gov, www.drugs.com, and www.clinicaltrials.gov (cutoff date: 19 July 2020)