Table 1.
Tyrosine kinase inhibitors (TKIs) evaluated in phase II and III clinical trials in the first line setting. † Updated analysis, after a median follow up of 34.5 months.
| TKIs | Sunitinib [97] | Pazopanib COMPARZ [98] | Tivozanib TIVO-1 [99] | Cabozantinib CABOSUN [101,102] |
|---|---|---|---|---|
| Treatment line | 1st | 1st | 1st | 1st |
| Study design | Phase III | Phase III Non inferiority |
Phase III | Phase II |
| N | 750 | 1110 | 517 | 157 |
| Comparator arm | IFN α | Sunitinib | Sorafenib | Sunitinib |
| ORR (%) | 31 vs. 6 | 31 vs. 25 | 33.1 vs. 23.4 | 20 vs. 9 |
| PFS (months) | 11 vs. 5 (HR 0.42; p < 0.001) |
8.4 vs. 9.5 (HR 1.05) |
11.9 vs. 9.1 (HR 0.79; p = 0.042) |
8.6 vs. 5.3 (HR 0.66; p = 0.012) |
| OS (months) | 26.4 vs. 21.8 (HR 0.82) |
28.4 vs. 29.3 (HR 0.91) |
29.3 vs. 28.8 (HR 1.24; p = 0.105) |
26.6 vs. 21.2 (HR 0.80) † |
| Adverse events | Hypertension, Diarrhea, Fatigue, HFS, Leukopenia, Thrombocytopenia |
Fatigue, PPE AST, ALT, Br increase |
Hypertension, Dysphonia | Hypertension, Diarrhea, Anorexia, PPE, Weight loss |
| Approval regulatory authorities | 2006 (FDA) 2006 (EMA) |
2009 (FDA) 2010 (EMA) |
2017 (EMA) | 2017 (FDA) 2018 (EMA) |