Table 2.
Current status of antiangiogenic agents in CM
| Drugs affecting angiogenesis | Angiogenic Targets | Main Clinical Studies | Clinical Trial Identifiers |
|---|---|---|---|
| Bevacizumab | VEGF-A |
Corrie et al. 2019 [141] Fane et al. 2020 [139] |
|
| Bevacizumab + IFN-α2b | VEGF-A + bFGF | Grignol et al. 2011 [142] | |
| Nab-paclitaxel + Bevacizumab + Ipilimumab | VEGF-A | Markovic et al. 2020 [140] | |
| Carboplatin, Paclitaxel, and Bevacizumab ± Everolimus | VEGF-A | McWilliams et al. 2018 [143] | |
| Ipilimumab + Bevacizumab | VEGF-A | Phase I NCT00790010 | |
| Ipilimumab ± Bevacizumab | VEGF-A | Phase II NCT01950390 | |
| Pazopanib + Paclitaxel | VEGFR − 1, −2, −3 | Fruehauf et al. 2018 [145] | |
| Aflibercept | VEGF-A, −B, PlGF | Tarhini et al. 2011 [146, 193] | Phase II NCT00450255 |
| Aflibercept ± HD IL-2 | VEGF-A, −B, PlGF | Tarhini et al. 2018 [147] | Phase II NCT01258855 |
| Aflibercept + Pembrolizumab | VEGF-A, −B, PlGF | Phase I NCT02298959 | |
| Thalidomide | VEGF-A + TNF | Pawlak et al. 2004 [148] | |
| Thalidomide + Temozolamide | VEGF-A + TNFα | Clark et al. 2010 [149] |
Phase II NCT00072163, Phase II NCT00005815, Phase II NCT00104988 |
|
Thalidomide + Temozolamide +Lomustine |
VEGF-A + TNFα |
Phase I NCT00527657, Phase II NCT00072345 |
|
| Thalidomide + DTIC | VEGF-A + TNFα | Ott et al. 2009 [150] | Phase II NCT00006200 |
| Thalidomide + Semaxanib | VEGF-A + TNFα + VEGFR-2 + KIT | Phase II, NCT00017316 | |
| Thalidomide + IFN-α2b | VEGF-A + TNFα + bFGF | Phase II NCT00026520 | |
| Thalidomide + PEG-IFN-α2b | VEGF-A + TNFα + bFGF | Phase II NCT00238329 | |
| Lenalidomide | VEGF, VEGFR-2 | Eisen et al. 2010 [151] | |
| Lenalidomide + DTIC | VEGF, VEGFR-2 | Hwu et al. 2010 [152] | |
| Imatinib mesylate | PDGFR, KIT |
Ugurel et al. 2005 [156] Carvajal et al. 2011 [157] |
Phase II NCT00881049, Phase II NCT00154388 |
| Imatinib mesylate + Bevacizumab | VEGF, PDGFR, KIT | Flaherty et al. 2015 [155] | |
| Imatinib mesylate + Pembrolizumab | VEGF, PDGFR, KIT | Phase II NCT04546074 | |
| Imatinib mesylate + Binimetinib | VEGF, PDGFR, KIT | Phase II NCT04598009 | |
| Nilotinib | PDGFR, KIT | Guo et al. 2017 [159] | |
| Axitinib | VEGFR − 1, −2, −3 | Fruehauf et al. 2011 [161] | |
| Axitinib + Paclitaxel/Carboplatin | VEGFR − 1, − 2, − 3 | Algazi et al. 2015 [162] | |
| Axitinib + Nivolumab | VEGFR − 1, − 2, − 3 | Phase II NCT04493203 | |
| Axitinib + Toripalimab | VEGFR − 1, − 2, − 3 | Phase Ib NCT03086174 | |
| Endostatin + DTIC | VEGF, VEGFR and bFGF | Cui et al. 2013 [163] | |
| Sorafenib + DTIC | VEGFR-1–3, PDGFR-β, KIT | Eisen et al. 2011 | |
| Sorafenib + Temsirolimus or Tipifarnib | VEGFR-1–3, PDGFR-β, KIT | Margolin et al. 2012 [165] | |
| Sorafenib + Lenalidomide | VEGFR-1–3, PDGFR-β, KIT + VEGF + VEGFR-2 | Ganesan et al. 2014 [153] | |
| Sorafenib + Temozolomide | VEGFR-1–3, PDGFR-β, KIT | Phase II NCT00602576 | |
| Sorafenib + PEG-IFN-α2b | VEGFR-1–3, PDGFR-β, KIT + VEGF + bFGF | Phase II NCT00623402 | |
| Sorafenib + Bevacizumab | VEGF-A + VEGFR-1–3, PDGFR-β, KIT | Mahalingam et al. 2014 [166] | |
| Ramucirumab ± DTIC | VEGFR-2 | Carvajal et al. 2014 [144] | |
| Bevacizumab + Lenalidomide, Sorafenib,Temsirolimus, 5-fluorouracil, Leucovorin, or Oxaliplatin (FOLFOX) | VEGF + VEGFR-2+ VEGFR-1–3, | Phase I NCT01183663 | |
| Sunitinib | PDGFR-β, KIT |
Phase II NCT00462982 Phase II NCT02465060 (MATCH TRIAL) |
|
| Cabozantenib + Nivolumab/Ipilimumab | VEGFR-2, c-Met, KIT | Phase II NCT04091750 | |
| Cabozantenib + Nivolumab | VEGFR-2, c-Met, KIT | Phase I NCT04514484 | |
| Cabozantenib + Pembrolizumab | VEGFR-2, c-Met, KIT | Phase II NCT03957551 |
Abbreviations: bFGF basic fibroblast growth factor, TNFα tumor necrosis factor alpha, PIGF placental growth factor, HD high dose, DTIC Decarbazine, PEG-interferon Pegylated Interferon