Table 2.

Src inhibitor trials in breast cancer

Compound	Substrates	FDA status	Metastatic Breast Cancer Trials
			Trials:	Outcomes:	Toxicities:	Ref:
Dasatinib	Src family, c-kit, PDGFR, Bcr-Abl and ephrin receptor kinases	Approved for CML and Ph+ALL	Ph II: randomized letrozole=dasatinib for HR+, HER2- postmenopausal women with unresectable, locally recurrent or metastatic BC (NCT00696072)	Active, not recruiting		[172]
			Ph I/II: dasatinib+trastuzumab and paclitaxel in HER2+ metastatic BC (NCT01306942)	Recruiting		[172]
			Ph II: dasatinib monotherapy in advanced BC (NCT00546104)	Early closure, n=31, no significant effect in heavily treated MBC	Nausea (61 %), pleural effusions (52 %), fatigue (52 %), rash (52 %), diarrhea (48 %), and anorexia (42 %)	[173]
			Ph II: dasatinib monotherapy in metastatic TNBC(NCT00371254)	RR 5 %, PR in 2, SD in 11 of 43 evaluable patients	Fatigue (54 %), nausea (54 %), dyspnea 43 %), diarrhea (38 %), pleural effusion (36 %), rash (36 %)	[174]
			Ph II: dasatinib monotherapy in advanced HR+±HER2+ BC (NCT00371345)	Of 69 evaluable patients, 3 PR and 6 SD ≥16w. Disease control rate=13.0 %	Fatigue/asthenia, gastrointestinal symptoms, headache, pleural effusion, and rash	[175]
			Ph I: dasatinib plus paclitaxel in MBC (NCT00820170)	Of 13 evaluable patients, 4 PR (31 %) and 5 SD (29 %)	Rash, fatigue, diarrhea	[176]
			Ph II: randomized exemestaneidasatinib in advanced HR+BC (NCT00767520)	PFS 18. lw vs 16. lw with or without dasatinib, respectively,p=0.148	Unspecified	[172]
			Phl/II: dasatinib plus zoledronic acid in MBC tobones(NCT00566618)	Active, not recruiting		[172]
			Ph I/II: dasatinib plus ixabepilone in 2nd-or 3rd-line MBC (NCT00924352)	Completed, no results		[172]
Bosutinib	Src, Abl	Approved for Ph+CML	Ph II: bosutinib monotherapy in MBC (NCT00319254)	N=73, PFS 39.6 % at 16w, 2 years OSR 26.4 %, clinical benefit rate 27.4 % (PR+SD)	Diarrhea (66 %), nausea (55 %), vomiting (47 %)	[177]
			Ph II: randomized exemestaneibosutinib in postmenopausal women HR+, HER2- advanced BC (NCT00793546)	Early termination, unfavorable risk/benefit		[172]
			Ph I/II: capecitabine plus bosutinib in solid tumors (NCT00959946)	Early termination, unfavorable risk/benefit		[172]
			Ph II: randomized letrozole=bosutinib in postmenopausal women with HR+, HER2- advanced BC (NCT00880009)	Early termination, unfavorable risk/benefit		[172]
Saracatinib	Src, Abl	No approval	Ph II: saracatinib in HR- advanced BC (NCT00559507)	n=9, 3SD and 6PD in <6 m	Fatigue (78 %), nausea (44 %)	[178]
			Ph I/II: randomized neoadjuvant anastrazoleisaracatinib in postmenopausal women with HR+BC (NCT01216176)	Recruiting		[172]

BC breast cancer, HR hormone receptor, MBC metastatic breast cancer, OS overall survival, PD progressive disease, RR response rate, SD stable disease, TNBC triple-negative breast cancer