Table 2.
Results of main randomized controlled trials worldwide as first-line and second-line treatment for patients with advanced HCC: Sorafenib-era.
| Agents | n | RR (%) | DCR (%) | TTP/PFS (Median: Months) | Hazard Ratio (95% CI) | p-value | OS (Median: Months) | Hazard Ratio (95%CI) | p-value | Phase/Name of Trial | Authors Reported Year | Reference No. | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Line Chemotherapy | |||||||||||||
| Sunitinib | 530 | 6.6% | 50.8% | 3.6 | 1.13 (0.99–1.30) | 0.2286 | 7.9 | 1.30 (1.13–1.50) | 0.0014 | Phase III | Cheng AL | ||
| Sorafenib | 542 | 6.1% | 51.5% | 3.0 | - | 10.2 | SUN1170 | 2013 | [43] | ||||
| Brivanib | 577 | 12% | 66% | 4.2 | 1.01 (0.88–1.16) | 0.8532 | 9.5 | 1.06 (0.93–1.22) * | 0.3730 | Phase III | Jofnson P | ||
| Sorafenib | 578 | 9% | 65% | 4.1 | - | 9.9 | - | BRISK-FL | 2013 | [44] | |||
| Linifanib | 514 | 13.0% | ND | 5.4 | 0.759 (0.643–0.895) | 0.001 | 9.1 | 1.046 (0.896–1.221) | ND | Phase III | Cainap C | ||
| Sorafenib | 521 | 6.9% | ND | 4.0 | - | 9.8 | - | LiGHT | 2015 | [45] | |||
| Sorafenib + Erlotinib | 362 | 6.6% | 43.9% | 3.2 | 1.135 (0.944–1.366) | 0.18 | 9.5 | 0.929 (0.781–1.106) | 0.408 | Phase III | Zhu AX | ||
| Sorafenib + Placebo | 358 | 3.9% | 52.5% | 4.0 | - | 8.5 | - | SEARCH | 2015 | [46] | |||
| Vandetanib (10 mg) | 25 | 0.0% | 5.3% | 1.70 | 0.64 (0.35–1.18) | 0.15 | 5.75 | 0.44 (0.22–0.86) | 0.02 | Phase II | |||
| Vandetanib (300 mg) | 19 | 0.0% | 16.0% | 1.05 | 0.71 (0.38–1.36) | 0.31 | 5.95 | 0.60 (0.30–1.19) | 0.15 | Hsu C | |||
| Placebo | 23 | 0.0% | 8.7% | 0.95 | - | 4.27 | - | 2012 | [47] | ||||
| Nintedanib | 63 | 6.3% | 68.3% | 2.8 | 1.21 (0.73–2.01) | ND | 10.2 | 0.94 (0.59–1.49) | ND | Phase II | Cheng AL | ||
| Sorafenib | 32 | 3.1% | 84.4% | 3.7 | 10.7 | - | 2015 | [48] | |||||
| Nintedanib | 62 | 1.6% | 82.3% | 5.5 | 1.44 (0.81–2.57) | ND | 11.9 | 0.88 (0.52–1.47) | ND | Phase II | Palmer D | ||
| Sorafenib | 31 | 6.5% | 90.3% | 4.6 | 11.4 | - | 2015 | [49] | |||||
| Dovitinib | 82 | 6.1% | 57.3% | 4.1 | 1.42 (0.98–2.08) | ND | 8.0 | 1.27 (0.90–1.79) | ND | Phase II | Cheng AL | ||
| Sorafenib | 83 | 10.8% | 63.9% | 4.1 | 8.5 | 2015 | [50] | ||||||
| Sorafenib + Doxorubicin | 47 | 4% | NA | 6.4 | 0.5 (0.3–0.9) | 0.02 | 13.7 | 0.49 (0.3–0.8) | 0.006 | Phase II | Abou-Alfa GK | ||
| Doxorubicin | 49 | 2% | NA | 2.8 | - | 6.5 | - | 2010 | [51] | ||||
| Second Line Chemotherapy | |||||||||||||
| Brivanib | 263 | 10% | 61% | 4.2 | 0.56 (0.42–0.76) | <0.001 | 9.4 | 0.89 (0.69–1.15) * | 0.3307 | Phase III | Llovet JM | ||
| Placebo | 132 | 2% | 40% | 2.7 | - | 8.2 | - | BRISK-PS | 2013 | [52] | |||
| Everolimus | 362 | 2.2% | 56.1% | 3.0 | 0.93 (0.75–1.15) | ND | 7.6 | 1.05 (0.86–1.27) | 0.68 | Phase III | Zhu AX | ||
| Placebo | 184 | 1.6% | 45.1% | 2.6 | 7.3 | - | EVOLVE-1 | 2014 | [53] | ||||
| S-1 | 222 | 5.4% | 43.2% | 2.6 | 0.60 (0.46–0.77) | <0.0001 | 11.1 | 0.86 (0.67–1.10) | 0.2201 | Phase III | Kudo M | ||
| Placebo | 111 | 0.9% | 24.3% | 1.4 | 11.2 | - | S-CUBE | 2015 | [54] | ||||
| Axitinib | 134 | 9.7% | 31.1% | 3.6 | 0.618 (0.438–0.871) | 0.0 | 12.7 | 0.870 (0.620–1.222) | 0.211 | Phase III | Kang YK | ||
| Placebo | 68 | 2.9% | 11.8% | 1.9 | 9.7 | - | 2014 | [55] | |||||
| GC33 | 121 | ND | ND | 2.6 | 0.98 | 0.93 | 6.8 | 0.99 | 0.97 | Phase II | Yen CJ | ||
| Placebo | 60 | ND | ND | 1.5 | 6.7 | - | 2014 | [56] | |||||
| Tigatuzumab (6/2 mg/kg) + Sorafenib | 53 | 5.7% | 54.8% | 3.0 | 1.12 (0.69–1.80) | 0.657 | 8.2 | ND | 0.303 | Phase II | |||
| Tigatuzumab (6/6 mg/kg) + Sorafenib | 54 | 14.8% | 68.5% | 3.9 | 1.15 (0.73–1.81) | 0.548 | 12.2 | ND | 0.659 | Cheng AL | |||
| Sorafenib | 55 | 11% | 54.6% | 2.8 | - | 8.2 | - | 2015 | [57] | ||||
* 95.8% confidence interval; 6/2 mg/kg, 6 mg/kg loading, 2 mg/kg/week maintenance; 6/6 mg/kg, mg/kg loading, 6 mg/kg/week maintenance. RR, response rate; DCR, diasease control rate; TTP, time to progression; PFS, prgresion free survival; OS, overall survival; ND, no data.