Emerging targeted combinations in the management of breast cancer

Figures & data

Figure 1 Human epidermal growth factor receptor (HER) and poly (ADP-ribose) polymerase (PARP).

Abbreviations: AKT, also known as Protein Kinase B (PKB), is a serine/threonine-specific protein kinase; Grb2, growth factor receptor-bound protein 2; HER, human epidermal growth factor receptor; MAPK, mitogen-activated protein kinases; MEK (aka MAP2K), mitogen-activated protein kinase kinase; mTOR, mammalian target of rapamycin; PARP, poly (ADP-ribose) polymerase (PARP); PI3k, phosphatidylinositol 3’-kinase; Raf, protooncogene cytoplasmic serine/threonine protein kinases; SOS, son of sevenless.

Table 1 Phase II studies examining erlotinib

Study	Treatment arms	Number per arm	ORR (CR/PR)	CBR (CR/PR/SD)	Median PFS/TTP (weeks)	Median OS (months)	Comment
Dickler et al^Citation30	Erlotinib/bevacizumab	37	3%	14%a	11	–
Kaur et al^Citation27	Erlotinib/weekly docetaxel	31	55%b	90%b	–	23b	Dose reduced due to hematological toxicity
Montagna et al^Citation28	Metronomic capecitabine and cyclophosphamide plus bevacizumab and erlotinib	26	62%c	75%c	TTP 43	–
Twelves et al^Citation29	Capecitabine/docetaxel/erlotinib	24	67%d	–	–	–	Dosing varied between three arms
Graham et al^Citation33	Gemcitabine/erlotinib	59	14%	–	2.8 months	–

Notes:

a At 26 weeks on the study

b 20 patients evaluable

c 24 patients evaluable

d 21 patients evaluable.

Abbreviations: CBR, clinical benefit rate; CR, complete response; ORR, objective response rate; OS, overall survival; PFS/TTP, progression free survival/time to progression; PR, partial response; SD, stable disease for 6 months.

Table 2 Phase II studies of tipifarnib in MBC

Study	Treatment arms	Number of patients per arm	ORR (CR/PR)	CBR	Median PFS/TTP (months)
Dalenc et al^Citation54	Tipifarnib/tamoxifen	20	5%	50%	5.7
Li et al^Citation55	Tipifarnib/capecitabine	63	9.5%	32%	2.6
Li et al^Citation56	Tipifarnib/fulvestrant	31	35.5%	51.6%	TTP 7.2
Johnston et al^Citation57	Tipifarnib/letrozole	80	30%	49%	TTP 5.6
	Letrozole/placebo	40	38%	62%	TTP 10.8

Abbreviations: CBR, clinical benefit rate; CR, complete response; MBC, metastatic breast cancer; ORR, objective response rate; PFS/TTP, progression free survival/time to progression; PR, partial response.

Figure 2 Role of VEGFR (vascular endothelial growth factor receptor) in vascularization/angiogenesis and its inhibitors.

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