Table 2.
Efficacy of TACE+apatinib versus TACE in treatment response, overall survival, progression-free survival, AFP, MMP9, and VEGF, which were analyzed by TACE agent classification, apatinib dosage, and trial type.
| Outcomes | Subgroups | Included studies | OR(95%CI) | p, I2 | p from meta-regression | p from publications bias | Grade |
|---|---|---|---|---|---|---|---|
| Treatment response (TR) | Overall | 38 | 2.005 (1.567, 2.564)* | 0.000, 55.6%# | 0.706, 0.466 | Low | |
| TACE agent classify | |||||||
| Adriamycin+platinum | 12 | 2.155 (1.289, 3.604)* | 0.000, 68.8%# | 0.429 | 0.411, 0.844 | Low | |
| Adriamycin+platinum+fluorouracin | 8 | 2.118 (1.427, 3.142)* | 0.277, 19.3% | 0.063, 0.504 | Moderate | ||
| Platinum+fluorouracin | 2 | 2.098 (1.082, 4.069)* | 0.328, 0.0% | – | Low | ||
| Platinum+raltitrexed | 3 | 1.807 (1.037, 3.150) | 0.609, 0.0% | 1.000, 0.155 | Low | ||
| Adriamycin+fluorouracin | 1 | 3.000 (0.507, 17.740) | – | – | Very low | ||
| Adriamycin | 8 | 2.089 (1.154, 3.781)* | 0.003, 67.0%# | 0.108, 0.593 | Low | ||
| Fluorouracil | 1 | 1.784 (0.616, 5.169) | – | – | Very low | ||
| No mention | 3 | 0.875 (0.131, 5.825) | 0.001, 84.9%# | 0.296, 0.192 | Very low | ||
| Apatinib dosage | |||||||
| 500 mg/day | 28 | 2.047 (1.488, 2.815)* | 0.000, 64.3%# | 0.640 | 0.407, 0.429 | Low | |
| >500 mg/day | 9 | 1.893 (1.359, 2.638)* | 0.556, 0.0% | 0.754, 0.671 | Moderate | ||
| <500 mg/day | 1 | 1.321 (0.469, 3.721) | – | – | Very low | ||
| Trial type | |||||||
| RCT | 15 | 2.414 (1.866, 3.122)* | 0.620, 0.0% | 0.277 | 0.656, 0.811 | High | |
| Retrospective study | 23 | 1.759 (1.214, 2.549)* | 0.000, 68.1%# | 0.616, 0.470 | Low | ||
| Overall survival(OS) | |||||||
| 6M-OS | Overall | 27 | 2.311 (1.744, 3.062)* | 0.228, 16.2% | 0.466,0.136 | Moderate | |
| TACE agent classify | |||||||
| Adriamycin+platinum | 9 | 2.219 (1.376, 3.579)* | 0.110, 38.7% | 0.505 | 0.251,0.139 | Moderate | |
| Adriamycin+platinum+fluorouracin | 7 | 2.666 (1.565, 4.540)* | 0.456, 0.0% | 0.230, 0.418 | Moderate | ||
| Platinum+raltitrexed | 3 | 11.748 (2.154, 64.078)* | 0.980, 0.0% | 0.602, – | Moderate | ||
| Adriamycin+fluoroura | 1 | 2.786 (0.773,10.043) | – | – | Very low | ||
| Adriamycin | 4 | 1.492 (0.584, 3.812) | 0.111, 50.1%# | 0.308, 0.077 | Low | ||
| Fluorouracil | 1 | 2.071 (0.178, 24.148) | – | – | Very low | ||
| No mention | 2 | 3.163 (1.124, 8.902)* | 0.496, 0.0% | – | Low | ||
| Apatinib dosage | |||||||
| 500 mg/day | 18 | 2.305 (1.604, 3.311)* | 0.157, 25.4% | 0.958 | 0.344, 0.138 | Moderate | |
| >500 mg/day | 7 | 2.676 (1.587, 4.511)* | 0.456, 0.0% | 0.099, 0.412 | Moderate | ||
| <500 mg/day | 2 | 2.311 (0.319, 16.754) | 0.175, 45.6% | – | Very low | ||
| Trial type | |||||||
| RCT | 9 | 2.804 (1.903, 4.132)* | 0.998, 0.0% | 0.233 | 0.532, 0.422 | Moderate | |
| Retrospective study | 18 | 2.187 (1.384, 3.454)* | 0.045, 39.3% | 0.256,0.105 | Moderate | ||
| 1Y-OS | Overall | 30 | 2.694 (2.050, 3.540)* | 0.000, 54.6%# | 0.035, 0.045¶ | Very low | |
| TACE agent classify | |||||||
| Adriamycin+platinum | 10 | 2.186 (1.352, 3.534)* | 0.007, 60.5%# | 0.703 | 0.032, 0.019¶ | Very low | |
| Adriamycin+platinum+fluorouracin | 7 | 2.123 (1.385, 3.253)* | 0.314, 15.2% | 0.536,0.746 | Low | ||
| Platinum+fluorouracin | 1 | 3.000 (0.993, 9.067) | – | – | Very low | ||
| Platinum+raltitrexed | 3 | 7.455 (3.524, 15.772)* | 0.251, 27.6% | 0.296, 0.058 | Very low | ||
| Adriamycin+fluoroura | 1 | 2.667 (0.648, 10.972) | – | – | Very low | ||
| Adriamycin | 5 | 4.055 (2.485, 6.618)* | 0.213, 31.3% | 0.734, 0.645 | Moderate | ||
| Fluorouracil | 1 | 1.833 (0.616, 5.453) | – | – | Very low | ||
| No mention | 2 | 1.273 (0.581, 2.793) | 0.617, 0.0% | – | Very low | ||
| Apatinib dosage | |||||||
| 500 mg/day | 21 | 3.046 (2.162, 4.293)* | 0.000, 61.3%# | 0.111 | 0.103, 0.043 | Low | |
| >500 mg/day | 8 | 2.159 (1.468, 3.174)* | 0.394, 4.7% | 0.108,0.274 | Moderate | ||
| <500 mg/day | 1 | 0.893(0.311, 2.561) | – | – | Very low | ||
| Trial type | |||||||
| RCT | 9 | 2.328(1.624, 3.336)* | 0.966, 0.0% | 0.608 | 0.095, 0.111 | Moderate | |
| Retrospective study | 21 | 2.870(1.983, 4.152)* | 0.000, 67.4%# | 0.061,0.074 | Low | ||
| Progression-free survival (PFS) | |||||||
| 6M-PFS | Overall | 17 | 2.783 (1.292, 5.996)* | 0.000, 85.6%# | 0.893, 0.310 | Low | |
| TACE agent classify | |||||||
| Adriamycin+platinum | 8 | 1.593 (0.484, 5.240) | 0.000, 85.7%# | 0.154 | 0.072,0.094 | Low | |
| Adriamycin+platinum+fluorouracin | 1 | 2.714 (0.494, 14.901) | – | – | Very low | ||
| Platinum+raltitrexed | 1 | 16.000 (5.443, 47.035)* | – | – | Very low | ||
| Adriamycin | 5 | 4.194 (1.721, 10.221)* | 0.023, 64.6%# | 0.806, 0.367 | Low | ||
| No mention | 2 | 4.105 (0.694, 24.264) | 0.067, 70.1%# | – | Very low | ||
| Apatinib dosage | |||||||
| 500 mg/day | 12 | 3.615 (1.597, 8.183)* | 0.000, 83.5%# | 0.167 | 0.493, 0.144 | Low | |
| >500 mg/day | 2 | 0.736 (0.063, 8.558) | 0.025, 80.2%# | – | Very low | ||
| <500 mg/day | 2 | 2.115( 0.040, 112.511) | 0.000, 96.2%# | – | Very low | ||
| Trial type | |||||||
| RCT | 4 | 2.171 (0.148, 31.785) | 0.000, 91.4%# | 0.788 | 0.602, 0.626 | Low | |
| Retrospective study | 13 | 2.926 (1.291, 6.627)* | 0.000, 85.6%# | 0.393,0.215 | Very low | ||
| 1Y-PFS | Overall | 17 | 3.837 (2.236, 6.583)* | 0.000, 69.3%# | 0.434, 0.823 | Low | |
| TACE agent classify | |||||||
| Adriamycin+platinum | 7 | 2.265 (0.783, 6.555) | 0.000, 78.7%# | 0.820 | 0.881,0.311 | Low | |
| Adriamycin+platinum+fluorouracin | 1 | 3.143 (1.120, 8.822)* | – | – | Very low | ||
| Platinum+raltitrexed | 1 | 10.872 (2.906, 40.673)* | – | – | Very low | ||
| Adriamycin | 6 | 6.528 (2.852, 14.944)* | 0.012, 66.1%# | 0.573,0.231 | Low | ||
| No mention | 2 | 1.941 (0.600, 6.287) | 0.231, 30.2% | – | Very low | ||
| Apatinib dosage | |||||||
| 500 mg/day | 13 | 4.291 (3.126, 5.889)* | 0.558, 0.0% | 0.634 | 0.143, 0.416 | Moderate | |
| >500 mg/day | 2 | 1.039 (0.113, 9.554) | 0.006, 86.9%# | – | Very low | ||
| <500 mg/day | 2 | 1.839 (0.000, 8073.995) | 0.000, 96.0%# | – | Very low | ||
| Trial type | |||||||
| RCT | 4 | 4.719 (0.673, 33.070) | 0.000, 90.5%# | 0.810 | 0.497,0.562 | Low | |
| Retrospective study | 13 | 3.821 (2.421, 6.031)* | 0.052, 42.6% | 0.625,0.373 | Moderate | ||
| AFP | Overall | 8 | −2.628 (−3.959, −1.296)* | 0.000, 97.4%# | 0.108,0.006¶ | Very low | |
| MMP9 | Overall | 6 | 1.650 (−0.370, 3.671) | 0.000, 98.2%# | 0.260,0.130 | Low | |
| VEGF | Overall | 8 | −1.317 (−2.897, 0.263) | 0.000, 97.9%# | 0.902,0.873 | Low | |
**Significant differences, #Substantial heterogeneity, ¶Publication bias.