Table 1.
Randomized clinical trial characteristics.
| Trial | NCT ID 1 Number Trial Phase | Cancer Type | Backbone Treatment Type | VEGF 2 Inhibitor (Dose) |
1st Line Treatment | Liver Metastases Only | Number of Patients with Liver Metastases | PFS 3 HR 4 (95%CI) |
OS 5 HR 4 (95% CI) |
|---|---|---|---|---|---|---|---|---|---|
| Escudier et al. JCO 2010 (AVOREN) [43] |
NCT02056587 III |
Renal Cell Carcinoma | Immunotherapy | Bevacizumab (10 mg/kg IV q2weekly) |
Yes | No | 138 | 1.61 (1.09–2.37) |
|
| Rini et al. JCO 2010 (CALGB 90206) [44] |
NCT00072046 III |
Renal Cell Carcinoma | Immunotherapy | Bevacizumab (10 mg/kg IV q2weekly) |
Yes | No | 147 | 0.727 (0.507–1.043) |
|
| Van Cutsem et al. JCO 2009 [47] | III | Pancreatic Cancer | Chemotherapy + Targeted therapy | Bevacizumab (5 mg/kg IV q2weekly) |
Yes | No | 462 | 0.83 (0.68–1.02) |
|
| Mir et al. Lancet Oncology 2016 (PAZOGIST) [48] |
NCT01323400 II |
GIST | Best supportive care | Pazopanib (800 mg PO OD) |
No | No | 34 | 0.29 (0.13–0.67) |
|
| Fuchs et al. Lancet Oncology 2019 (RAINFALL) [49] |
NCT02314117 III |
Gastric orJunctional Adenocarcinoma | Chemotherapy | Ramucirumab (8 mg/kg IV D1,8 q3weekly) |
Yes | No | 236 6 | 0.605 (0.433–0.847) |
0.907 (0.674–1.219) |
| Petrylak et al. JCO 2016 [45] |
NCT01282463 II |
Urothelial Carcinoma | Chemotherapy | Ramucirumab (10 mg/kg IV q3weekly) |
No | No | 28 | 0.59 (0.25–1.41) |
0.88 (0.39–1.96) |
| Petrylak et al. Lancet Oncology 2020 (RANGE) [46] |
NCT02426125 III |
Urothelial Carcinoma | Chemotherapy | Ramucirumab (10 mg/kg IV q3weekly) |
No | No | 147 | 0.885 (0.614–1.276) |
|
| Nakagawa et al. Lancet Oncology 2019 (RELAY) [37] |
NCT02411448 III |
Non-small Cell Lung Cancer | Targeted therapy | Ramucirumab (10 mg/kg IV q2weekly) |
Yes | No | 45 | 0.48 (0.23–1.02) |
|
| Tabernero et al. Clinical Cancer Research 2013 (RESPECT) [27] |
NCT00865709 II |
Colorectal Cancer | Chemotherapy | Sorafenib (400 mg PO BD) |
Yes | No | 160 | 0.86 (0.60–1.24) |
1.06 (0.72–1.56) |
| Escudier et al. NEJM 2007 (TARGET) [18] |
NCT00073307 III |
Renal Cell Carcinoma | Best supportive care | Sorafenib (400 mg PO BD) |
No | No | 233 | 0.44 7 (0.29–0.68) |
|
| Sandler et al. NEJM 2006. (NCT00021060) [38] |
NCT00021060 II/III |
Non-small Cell Lung Cancer | Chemotherapy | Bevacizumab (15 mg/kg IV q3weekly) |
Yes | No | 163 | 0.68 (0.49–0.96) |
|
| Scagliotti et al. JCO 2012 [39] |
NCT00457392 III |
Non-small Cell Lung Cancer | Targeted therapy | Sunitinib (37.5 mg PO OD) |
No | No | 182 | 0.957 (0.689–1.329) |
0.980 (0.711–1.351) |
| Cunningham et al. Lancet Oncology 2013. (AVEX) [28] |
NCT00484939 III |
Colorectal Cancer | Chemotherapy | Bevacizumab (7.5 mg/kg IV q3weekly) |
Yes | Yes | 106 | 0.54 (0.35–0.83) |
|
| Tabernero et al. EJC 2014 (VELOUR) [29] |
NCT00561470 III |
Colorectal Cancer | Chemotherapy | Aflibercept (4 mg/kg IV q2weekly) |
No | Yes | 299 | 0.547 (0.413–0.725) |
0.649 (0.492–0.855) |
| Tang et al. JCO 2020 (BECOME) [30] |
NCT01972490IV | Colorectal Cancer | Chemotherapy | Bevacizumab (5 mg/kg IV q2weekly) |
Yes | Yes | 241 | 0.49 (0.38–0.65) |
0.71 (0.52–0.97) |
| Tebbutt et al. JCO 2010 (MAX) [31] |
ACTRN12605000025639 | Colorectal Cancer | Chemotherapy | Bevacizumab (7.5 mg/kg IV q3weekly) |
Yes | Yes | 61 | 0.25 8 | |
| Li et al. Future Oncology 2018 [32] |
NCT01661270 III |
Colorectal Cancer | Chemotherapy | Aflibercept4 mg/kg IV q2weekly) | No | Yes | 71 | 0.54 (0.3–0.971) |
|
| Tabernero et al. Lancet Oncology 2015 (RAISE) [33] |
NCT01183780 III |
Colorectal Cancer | Chemotherapy | Ramucirumab (8 mg/kg IV q2weekly) |
No | Yes | 187 | 0.801 (0.590–1.089) |
0.963 (0.679–1.367) |
| Chi et al. The Oncologist 2021 (ALTER0703) [34] |
NCT02332499 II/III |
Colorectal Cancer | Chemotherapy | Anlotinib (12 mg PO D1-14 q3weekly) |
No | No | 312 | 0.27 (0.20–0.36) |
0.92 (0.71–1.2) |
| Doebele et al. Cancer 2015 [40] |
NCT01160744 II |
Non-small Cell Lung Cancer | Chemotherapy | Ramucirumab (10 mg/kg IV q3weekly) |
Yes | No | 24 | 0.45 9 (0.25–1.05) |
|
| Li et al. Jama 2018 (FRESCO) [35] |
NCT02314819 III |
Colorectal Cancer | Best supportive care | Fruquintinib (5 mg PO OD D1-21 q3weekly) |
No | No | 287 | 0.22 (0.17–0.30) |
0.59 (0.45–0.77) |
| Van Cutsem et al. Annals of Oncology 2018 (LUME-Colon 1) [36] |
NCT02149108 III |
Colorectal Cancer | Best supportive care | Nintedanib (200 mg PO BD) |
No | No | 543 | 0.53 (0.44–0.64) |
0.95 (0.79–1.14) |
| Zhao et al. Journal of Thoracic Oncology 2021 (CTONG1706) [41] |
NCT02824458 III |
Non-small Cell Lung Cancer | Targeted therapy | Apatinib (500 mg PO OD) |
Yes | No | 40 | 0.42 (0.15–1.17) |
|
| Kim et al. JCO 2012 (BEAM) [50] |
NCT00434252. II |
Melanoma | Chemotherapy | Bevacizumab (15 mg/kg IV q3weekly) |
Yes | No | 96 | 0.73 (0.46–1.16) | 0.60 (0.36–1.00) |
| Shen et al. Journal of Cancer Research and Clinical Oncology 2013 (ALTER 0303) [42] |
NCT02388919 III |
Non-small Cell Lung Cancer | Best supportive care | Anlotinib (12 mg PO OD) |
No | No | 78 | 0.23 (0.12–0.42) | 0.61 (0.36–1.02) |
1 NCT ID number, National Clinical Trials (NCT) identification number; 2 VEGF, vascular endothelial growth factor; 3 PFS, progression-free survival; 4 HR, hazard ratio; 5 OS, overall survival; 6 Fuchs et al., Lancet Oncology 2019 (RAINFALL)—number of patients with liver metastasis reported in OS analysis n = 236; number of patients with liver metastasis reported in PFS n = 189. 7 Escudier et al. NEJM 2007 (TARGET)—HR estimated from Figure 3 of the manuscript. 8 Tebbutt et al. JCO 2010 (MAX)—95% CI for HR for PFS was not provided in the manuscript. 9 Doebele et al. Cancer 2015—HR estimated from Figure 4 of the manuscript.