Table 2 Current status of antiangiogenic agents in CM

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