Table 1.
Targets and clinical outcomes of TKIs which have shown results in registered clinical trials of osteosarcoma treatment.
| TKIs | RTKs and IC50 (nM, mean) | Clinical outcome | References | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| VEGFR1 | VEGFR2 | VEGFR3 | KIT | RET | PDGFRα | PDGFRβ | FGFR1 | |||
| Apatinib | 70 | 1 | - | 429 | 13 | >1,000 | - | >1,0000 | PR rate 43% (16/37), 4-months PFS rate 56.76%, m-PFS 4.5 m. | (16, 17) |
| Axitinib | 0.1 | 0.2 | 0.29 | 1.7 | >1,000 | 5 | 1.6 | 231 | 5-months SD rate 100% (2/2). | (18, 19) |
| Cabozantinib | 12 | 0.035 | 6 | 4.6 | 5.2 | - | 234 | 5,294 | PR rate 12% (5/42), 6-months PFS rate 33%, m-PFS 6.2 m. | (20–22) |
| Cediranib | 5 | <1 | 3 | 2 | - | 36 | 5 | 26 | One of four patient had PR after two cycles. | (23, 24) |
| Imatinib | 19,500 | 10,700 | 5,700 | 97 | - | 72 | - | 31,200 | Five of 27 patients had SD at 4 months. | (25–27) |
| Lenvatinib | 4.7 | 3 | 2.3 | 85 | 6.4 | 29 | - | 61 | PR rate 8% (2/26), 4-months PFS rate 33%, m-PFS 3.4 m. | (28, 29) |
| Regorafenib | 13 | 4.2 | 46 | 7 | 1.5 | - | 22 | 202 | PR rate 8% (2/26), 12-weeks PFS rate 62%, m-PFS 16.4 w. | (30, 31) |
| Sorafenib | - | 4 | 20 | 68 | 0.4 | 18 | 57 | 580 | PR rate 9% (3/35), 4-months PFS rate 46%, m-PFS 4 m. | (32–34) |
PFS, progression-free survival; TKI, tyrosine kinase inhibitor; RTKs, receptor tyrosine kinases; PR, partial response; VEGFR, vascular endothelial growth factor receptor; KIT, stem cell factor receptor; RET, rearranged during transfection; FGFR1, fibroblast growth factor receptor; PDGFR, platelet-derived growth factor receptor; SD, stable disease.