Table 2. Antiangiogenic agents trialed in soft tissue sarcoma.

Antiangiogenic agents divided by their mode of action. Their targets are reported. In addition, the results of completed clinical trials or the presence of ongoing clinical trials are reported. (+) positive results, (−) negative results, (=) not properly clear results and (X) no results published. VEGF, vascular endothelial growth factor; PDGFR, platelet-derived growth factor receptor; IGF-1R, insulin growth factor receptor; DR, death receptor; VEGFR, vascular endothelial growth factor receptor; FGFR, fibroblast growth factor receptor; EGFR, epidermal growth factor receptor; FKBP12, FK506 binding protein; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; IL, interleukin.

Mode of action	Drug	Target	Response	Comments	Reference(s)
Monoclonal antibody	Bevacizumab	VEGF	+	Bevacizumab in combination with other drugs; often the benefit of adding bevacizumab remains unclear	[66–70]
	IMC-3G3	PDGFRα	+	Only Phase I studies results available. A Phase Ib/II study is ongoing (NCT01185964)	[71]
	TRC105	CD105	X	A Phase 1B Dose-escalation Study of TRC105 in Combination With Pazopanib is ongoing (NCT0197551)	[72]
	Cixutumumab	IGF-1R	+		[73–77]
	Figitumumab	IGF-1R	+	Only Phase I studies results available	[78,79]
	AMG 479	IGF-1R	+	Open Label Extension Study (Phase II) of AMG 479 and AMG 479 (NCT01327612)	[80,81]
	AMG 655	DR 5	+	Open Label Extension Study (Phase II) of AMG 479 and AMG 479 (NCT01327612)	[82]
	Vitaxin	Integrin αVβ3	=	Safe and potentially active Only few cases of soft tissue sarcoma analysed	[83–85]
Tyrosine kinase inhibitor	Sunitinib	VEGFR-1, VEGFR-2,VEGFR-3,PDGFR-α/β, KIT	+	Sunitinib demonstrated notable evidence of metabolic response in several patients with non-GIST sarcoma but a deeper subtypes stratification is needed	[86–89]
	Sorafenib	VEGFR-2,VEGFR-3,PDGFR,c-RAS, b-RAF,KIT	+		[90–93]
	Pazopanib	VEGFR-1, VEGFR-2,VEGFR-3,PDGFR-α/β, KIT	+		[94–97]
	Dasatinib	VEGFR-2, PDGFR, BCR/ABL, Src and KIT	X	Three active clinical trials (NCT00464620, NCT01643278 and NCT00788125
	Brivanib	VEGF-R2 and FGF-R1 and -2	X	Clinical trial NCT00633789, completed
	Cediranib	VEGFR-1,VEGFR-2, VEGFR-3	+	Single-agent activity on alveolar soft part sarcoma. A phase II trial (NCT01391962) is currently being conducted for patients with alveolar soft part sarcoma comparing cediranib with sunitinib	[98,99]
	Tivantinib	c-Met	X	Phase Ib Study of the Combination of Pazopanib, and Tivantinib, in Patients With Refractory Advanced Solid Tumours (NCT01468922)	[100]
	Axitinib	VEGFR-1,VEGFR-2,VEGFR-3,PDGFR and c-KIT	X	Phase II study (NCT01140737)
	Semaxanib	VEGFR-2, KIT	−	No other ongoing clinical studies	[101]
	Cabozantinib	MET,VEGFR-2, RET	X	One Phase II ongoing clinical study (NCT01755195)
	Saracatinib	src	X	One Phase II clinical trial completed (NCT00659360)
	Gefitinib	EGFR, HER1	−	Gefitinib did not demonstrate sufficient activity	[102,103]
	Regorafenib	VEGFR and Tie-2	X	Three Phase II clinical trials ongoing (NCT01900743 NCT02048371 NCT02048722)
Rapalogues (mTORC1 tyrosine kinase inhibitors)	Temsirolimus	FKBP12	+	Temsirolimus has limited clinical activity. The oucomes can be improved by a combinatorial therapy	[74,76,104,105]
	Sirolimus	FKBP12	−	Objective tumour response was infrequent	[106]
	Ridaforolimus	FKBP12	+		[107–109]
	Everolimus	FKBP12	+	Phase II clinical study in combination with Imatinib (NCT01281865) Phase II clinical study ongoing in Children and Adolescents (NCT01216839)	[78]
Other	ABT-510	VEGF, bFGF, HGF, IL8	+	Thrombospondin analogue; Strong single-agent activity need to be more clarify.	[110–112]
	Aflibercept (VEGF Trap)	VEGF	+	Soluble decoy receptor. Modest activity Active a Phase II clinical trial (NCT00390234)	[113,114]