Skip to main content

Table 1 Combinations of endocrine therapies with biological agents: completed trials in ER+ and/or PgR+ breast cancer

From: Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer

Clinical setting

Trial phase

Intervention

Clinical endpoints

Biological correlates

Ref.

MBC: hormone-refractory

II (N = 15)

ANA + GEF

PR = 0

SD = 0

NA

[19]

Neoadjuvant PBC

II RCT (N = 188)

ANA versus ANA + GEF for 16 weeks

ORR = 61% versus 48%, p = 0.067

Reduction in Ki67 = 83.6% versus 77.4%, p = 0.164

[20]

Preoperative PBC: EGFR+ only

II RT (N = 56)

GEF versus GEF + ANA for 4–6 weeks

ORR = 50% versus 54%

Reduction in Ki67 = 92.4% versus 98%, p = 0.005 Reduction in pER, pMAPK and pEGFR similar in both groups

[21]

Combination with trastuzumab

HER2+ MBC (note: all patients were TRAS and AI naïve, 18% were IHC2+/FISH-)

II (N = 33)

TRAS + LET

PR = 26%

SD = 26%

NA

[29]

HER2 MBC (all patients were IHC 3+ or FISH+)

III RCT (N = 207)

ANA versus ANA + TRAS

PFS = 2.4 months versus 4.8 months, p = 0.0016 OS = 23.9 months versus 28.5 months, p = 0.325 Among 147 evaluable patients: ORR = 6.8% versus 20.3%, p = 0.018

NA

[31]

Combination with lapatinib

MBC: included other hormone sensitive advanced cancers

I (N = 17)

LAP + LET

4 SD including 1 breast cancer

NA

[36]

Combination with farnesyltransferase inhibitors: tipifarnib

MBC: hormone resistant

I (N = 12)

TAM + TIP

PR = 2/12

SD > 6 months = 1/12

NA

[42]

MBC: tamoxifen resistant

I (N = 20)

TAM + TIP

PR = 1/20

SD > 4 months = 6/20

SD > 6 months = 4/20

NA

[41]

MBC: tamoxifen resistant

II RCT (N = 120)

LET versus

PR = 38% versus 30%

NA

[43]

  

LET + TIP

SD = 38% versus 39%

  

Combination with mTOR inhibitors: everolimus and temsirolimus

MBC: stable or slowly progressing on letrozole.

Ib (N = 9)

LET + EVE 1, 5 or10 mg daily

No grade 3–4 toxicitiesat 5 mg (6 patients) or10 mg (3 patients)

NA

[50]

MBC

II (N = 92)

LET versusLET+TEM 10 mgdaily versusLET+TEM 30 mgintermittent

ORR = 45% versus33% versus 40%PFS = 11.6 monthsversus 11.5 monthsversus 13.2 months

NA

[51]

MBC

III RCT (N = 992)

LET versusLET + TEM intermittent

ORR = 24% versus 24%SD = 19% versus 16%PFS = 9.2 months versus9.2 months

NA

[52]

Combination with angiogenesis inhibitors: bevacizumab

MBC

II (N = 25)

LET + BEV

PR = 2/25SD > 6 months = 13/25SD < 6 months = 4/25PD = 6/25

NA

[57]

  1. AI, aromatase inhibitor; ANA, anastrozole; BEV, bevacizumab; ER, estrogen receptor; EVE, everolimus; FISH, fluorescent in situ hybridization; GEF, gefitinib; HER, human epidermal receptor; IHN, immunohistochemistry; LAP, lapatinib; LET, letrozole; MBC, metastatic breast cancer; mTOR, mammalian target of rapamycin; NA, none available; ORR, objective response rate (PR + clinical benefit rate); OS, overall survival; PBC, primary breast cancer; PD, progressive disease; pEGFR, phosphorylated endothelial growth factor receptor; pER, phosphorylated ER; PFS, progression free survival; PgR, progesterone; pMAPK, phosphorylated mitinogen activated protein kinase; PR, partial response; RCT, randomized controlled trial; RT, randomized trial; SD, stable disease; TAM, tamoxifen; TEM, temsirolimus; TIP, tipifarnib; TRAS, trastuzumab.