Table 2.
Tyrosine Kinase Inhibitors Currently in Clinical Development for Glioblastoma
| Drug | Mechanism | Phase | Disease Type | Response Rate (%) | PFS (months) | PFS6 (%) | OS (months) | Combination | Reference | ClinicalTrials.gov No. |
|---|---|---|---|---|---|---|---|---|---|---|
| Cediranib (AZD2171) | VEGFR1-3, PDGFR-β, c-kit TKI | II | rGBM | 27 (Macdonald) | 25.8 | 7.5 | — | Batchelor et al69 | ||
| Cediranib (AZD2171) | VEGFR1-3, PDGFR-β, c-kit TKI | II | rGBM | 56.7 (volumetric) | 25.8 | 7.5 | — | Batchelor et al69 | ||
| Cediranib (AZD2171) | VEGFR1-3, PDGFR-β, c-kit TKI | III | rGBM | — | 16 | — | — | Batchelor et al14 | ||
| Cediranib (AZD2171) | VEGFR1-3, PDGFR-β, c-kit TKI | III | rGBM | — | 34.5 | — | Lomustine | Batchelor et al14 | ||
| Cediranib (AZD2171) | VEGFR1-3, PDGFR-β, c-kit TKI | II* | nGBM | Temozolomide, radiotherapy | NCT01062425 | |||||
| Vatalanib (PTK787) | VEGFR1-3, PDGFR-β, c-kit TKI | I/II | rGBM | — | 25 | 11.1 | Imatinib, hydroxyurea | Reardon et al72 | ||
| Vatalanib (PTK787) | VEGFR1-3, PDGFR-β, c-kit TKI | I/II | rGBM | 8.1 | Temozolomide | Reardon et al175 | ||||
| Vatalanib (PTK787) | VEGFR1-3, PDGFR-β, c-kit TKI | I/II | rGBM | 4.3 | Lomustine | Reardon et al175 | ||||
| Vatalanib (PTK787) | VEGFR1-3, PDGFR-β, c-kit TKI | I | nGBM | 15 | 7.2 | 16.2 | Temozolomide, radiotherapy | Gerstner et al73 | ||
| Vatalanib (PTK787) | VEGFR1-3, PDGFR-β, c-kit TKI | I/II | nGBM | — | 6.8 | 63.2 | 17.3 | Temozolomide, radiotherapy | Brandes et al74 | |
| Pazopanib (GW786034) | VEGFR1-3, PDGFR-α, PDGFR-β, c-Kit TKI | II | rGBM | 5.9 | 3 | 8.1 | — | Iwamoto et al75 | ||
| Pazopanib (GW786034) | VEGFR1-3, PDGFR-α, PDGFR-β, c-Kit TKI | II* | rGBM | Topotecan | NCT01931098 | |||||
| Cabozantanib (XL-184) | VEGFR-2, c-Met TKI | II | rGBM | 21 | — | — | — | — | Wen et al210 | |
| Cabozantanib (XL-184) | VEGFR-2, c-Met TKI | II | rGBM | 30 | — | — | — | — | Wen et al210 | |
| Cabozantanib (XL-184) | VEGFR-2, c-Met TKI | II* | rGBM | — | NCT00704288 | |||||
| Cabozantanib (XL-184) | VEGFR-2, c-Met TKI | II* | rGBM | — | NCT01068782 | |||||
| Cabozantanib (XL-184) | VEGFR-2, c-Met TKI | I* | nGBM | — | NCT00960492 | |||||
| Sunitinib | VEGR2, PDGFR-α, PDGFR-β, c-Kit, FLT-3 TKI | II | rGBM | 0 | — | — | — | Neyns et al77 | ||
| Sunitinib | VEGR2, PDGFR-α, PDGFR-β, c-Kit, FLT-3 TKI | II | rGBM | 0 | — | 16.7 | 12.6 | — | Pan et al78 | |
| Sunitinib | VEGR2, PDGFR-α, PDGFR-β, c-Kit, FLT-3 TKI | II | rGBM | 10 | 10.4 | 9.4 | — | Kreisl et al76 | ||
| Sunitinib | VEGR2, PDGFR-α, PDGFR-β, c-Kit, FLT-3 TKI | II | rGBM | 0 | 0 | 4.4 | — | Kreisl et al76 | ||
| Sunitinib | VEGR2, PDGFR-α, PDGFR-β, c-Kit, FLT-3 TKI | I | rGBM | 24* | 12.2* | Irinotecan | Reardon et al90 | |||
| Sorafenib | VEGFR-2, Raf-1, PDGFR, c-Kit, Flt-3 TKI | II | rGBM | 3 | — | 9.4 | 9.7 | Temozolomide | Reardon et al177 | |
| Sorafenib | VEGR-2, PDGFR-α, PDGFR-β, c-Kit, FLT3 TKI | I/II | rGBM | 12 | — | 0 | — | Temsirolimus | Lee et al80 | |
| Sorafenib | VEGR-2, PDGFR-α, PDGFR-β, c-Kit, FLT-3 TKI | II | rGBM | 5 | — | 14 | 5.7 | Erlotinib | Peereboom et al81 | |
| Sorafenib | VEGR-2, PDGFR-α, PDGFR-β, c-Kit, FLT-3 TKI | II | nGBM | 13 | 6 | — | 12 | Temozolomide | Hainsworth et al178 | |
| Vandetanib | VEGFR-2, EGFR | I/II | rGBM | 12.5 | — | 6.5 | 6.3 | — | Kreisl et al176 | |
| Vandetanib | VEGFR-2, EGFR | I | nGBM | 0 | 8 | 11 | Temozolomide, radiotherapy | Drappatz et al179 | ||
| Vandetanib | VEGFR-2, EGFR | I* | rGBM | Sirolimus | NCT00821080 | |||||
| AEE788 | VEGFR, EGFR | I | rGBM | 0 | — | — | — | — | Reardon et al106 | |
| Lenvatinib (E7080) * | VEGFR-2, VEGFR-3, FGFR1, c-kit, PDGFR-β | I/II* | rGBM | NCT01433991 | ||||||
| Tivozanib | VEGR-3 | II | rGBM | NCT01846871 | ||||||
| Enzastaurin | PKCβ, PI3K/AKT/mTOR | III* | rGBM | 2.9 | 11.1 | 6.6 | — | Wick et al15 |
Abbreviations: : EGFR, endothelial growth factor receptor; FGFR1, fibroblast growth factor receptor 1; FLT-3/Flt-3, fms-like tyrosine kinase 3; mTOR, mammalian target of rapamycin; nGBM, newly diagnosed glioblastoma; OS, overall survival; PDGFR, platelet-derived growth factor receptor; PFS, progression-free survival; PFS6, 6-month PFS; PI3K, phosphatidylinositol 3′-kinase; PKCβ, protein kinase C beta; rGBM, recurrent glioblastoma; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor.
*
Ongoing trial.
†
For overall group.