Table 1.
Anti-VEGF TKIs.
| Agent | Trial | Phase | Number | Patient | Therapy | Dosing | Results a vs. b |
|---|---|---|---|---|---|---|---|
| Sorafenib | Abou-Alfa et al. (2006) [51] | II | 137 | No prior systemic therapy | a. Sorafenib (n = 137) | Sorafenib 400 mg BID | OS: 9.2 months; TTP: 4.2 months; ORR: 8%; DCR: 41.6% |
| Abdel-Rahman et al. (2013) [33] | II | 52 | No prior systemic therapy | a. Sorafenib (n = 26); b. Capecitabine (n = 26) |
Sorafenib 400 mg BID; Capecitabine 1000 mg/m2 BID | OS: 7.05 months vs. 5.07 months, p < 0.016; PFS: 6 months vs. 4 months, p < 0.005; ORR: 15.5% vs. 3% | |
| SHARP (2008) [52] | III | 602 | No prior systemic therapy | a. Sorafenib (n = 299); b. Placebo (n = 303) |
Sorafenib 400 mg BID | OS: 10.7 months vs 7.9 months, HR 0.69, p < 0.001; TTP: 4.1 months vs. 4.9 months, p = 0.77; ORR: 2% vs. 1%; DCR: 43% vs. 32%, p = 0.002 | |
| Asia-Pacific (2009) [53] | III | 226 | No prior systemic therapy | a. Sorafenib (n = 150); b. Placebo (n = 76) |
Sorafenib 400 mg BID | OS: 6.5 months vs. 4.2 months, HR 68, p = 0.014; TTP: 2.8 months vs. 1.4 months, HR 0.57, p = 0.0005; ORR: 3.3% vs. 1.3%; DCR: 53% vs. 12%, p = 0.0019 | |
| Abou-Alfa et al. (2010) [54] | III | 96 | No prior systemic therapy | a. Sorafenib/Doxorubicin (n = 47); b. Doxorubicin/Placebo (n = 49) |
Sorafenib 400 mg BID; Doxorubicin 60 mg/m2 q21days | OS: 13.7 months vs. 6.5 months, HR 0.49, p = 0.006; PFS: 6 months vs. 2.7 months, p = 0.006; TTP: 6.4 months vs. 2.8 months, HR 0.5, p = 0.02; ORR: 4% vs. 2%; DCR: 62% vs. 29% | |
| CALGB-80802; (NCT01015833) | III | R | No prior systemic therapy | a. Sorafenib/Doxorubicin; b. Sorafenib |
Pending | ||
| BOOST; (NCT01405573) | III | R | No prior anti-angiogenesis, Child-Pugh B only | a. Sorafenib; b. Placebo |
Pending | ||
| Sunitinib | Zhu et al. (2009) [67] | II | 34 | No prior systemic therapy | a. Sunitinib (n = 34) | Sunitinib 50 mg daily, 4 weeks on, 2 weeks off | OS: 9.8 months; TTP: 4.1 months; ORR: 2.9%; DCR: 52.9% |
| Faivre et al. (2009) [68] | II | 37 | No prior systemic therapy | a. Sunitinib (n = 37) | Sunitinib 50 mg daily, 4 weeks on, 2 weeks off | OS: 8.0 months; PFS: 3.7 months; TTP: 5.3 months; ORR: 2.7%; DCR: 37.8% | |
| SAKK 77/06 (2010) [66] | II | 45 | No prior systemic therapy | a. Sunitinib (n = 45) | Sunitinib 37.5 mg daily | OS: 9.3 months; PFS: 1.5 months; TTP: 1.5 months; ORR: 2%; DCR: 42% | |
| Barone et al. (2013) [65] | II | 34 | No prior systemic therapy | a. Sunitinib (n = 34) | Sunitinib 50 mg daily, 4 weeks on, 2 weeks off | OS: 5.8 months; TTP: 2.8 months; ORR: 11.8%; DCR: 44% | |
| Linifanib | Toh et al. (2012) [72] | II | 44 | No prior systemic therapy | a. Llinifanib (n = 44) | Linifanib 0.25 mg/kg daily | OS: 9.7 months; TTP: 3.7 months; ORR: 9.1% |
| Cainap et al. (2015) [73] | III | 1035 | No prior systemic therapy | a. Linifanib (n = 530); b. Sorafenib (n = 544) |
Linifanib 17.5 mg daily; Sorafenib 400 mg BID | OS: 9.1 months vs. 9.8 months, HR 1.046; PFS: 4.2 months vs. 2.9 months, HR 0.813, p = 0.008; TTP: 5.4 months vs. 4.0 months, HR 0.895, p = 0.001; ORR: 10.1% vs. 6.1% | |
| Brivanib | BRISK-FL (2013) [76] | III | 1155 | No prior systemic therapy | a. Brivanib (n = 577); b. Sorafenib (n = 578) |
Brivanib 800 mg daily; Sorafenib 400 mg BID | OS: 9.5 months vs. 9.9 months, p = 0.3116; PFS: 4.2 months vs. 4.1 months, p = 0.8532); ORR: 12% vs. 9%, p = 0.0569; DCR: 66% vs. 65%, p = 0.8739 |
| BRISK-PS (2009) [77] | III | 395 | Failed sorafenib | a. Brivanib (n = 263); b. Placebo (n = 132) |
Brivanib 800 mg daily | OS: 9.4 months vs. 8.2 months, HR 0.89, p = 0.3307; TTP: 4.2 months vs. 2.7 months, p < 0.001; ORR: 10% vs. 2%; DCR: 61% vs. 40%, p < 0.001 | |
| Cediranib | Alberts et al. (2012) [79] | II | 28 | No prior systemic therapy | a. Cediranib (n = 28) | Cediranib 45 mg daily | OS: 5.8 months; TTP: 2.8 months; DCR: 25% |
| Zhu et al. (2013) [80] | II | 17 | Any line of therapy | a. Cediranib (n = 17) | Cediranib 30 mg daily | OS: 11.7 months; PFS: 5.3 months; DCR: 29% | |
| Regorafenib | Bruix et al. (2013) [94] | II | 36 | Failed sorafenib | a. Regorafenib (n = 36) | Regorafenib 160 mg daily, 3 weeks on, 1 week off | OS: 13.8 months; TTP: 4.3 months; ORR: 3%; DCR: 72% |
| RESORCE (NCT01774344) | III | R | Failed sorafenib | a. Regorafenib; b. Placebo |
Regorafenib 160 mg daily, 3 weeks on, 1 week off | Pending | |
| Orantinib | Kanai et al. (2011) [83] | I/II | 35 | Any line of therapy | a. Orantinib (n = 35) | Orantinib 400 mg BID | OS: 13.1 months; TTP: 2.1 months; ORR: 8.6%; DCR: 51.4% |
| Pazopanib | Yau et al. (2011) [90] | I | 26 | Prior therapy | a. Pazopanib (n = 26) | Pazopanib 200–800 mg daily | PFS: 17.7 weeks; ORR: 8%; DCR: 73% |
OS: median overall survival; PFS: median progression free survival; TTP: median time to progression; ORR: objective response rate; DCR: disease control rate.