Table 2

Endocrine/biological combinations: ongoing or recently closed trials in ER and/or PgR+ breast cancer

Clinical setting

Trial phase

Intervention

N

Biological endpoints

NCT protocol #

With EGFR inhibitors: gefitinib (GEF) or erlotinib (ERL)

Neoadjuvant PBC: (HER2+ only)

II

GEF × 2 weeks followed by GEF+TAM

45

Tumor biomarker analysis at weeks 1, 2, 6 and surgery

00206492

Neoadjuvant PBC

II

ANA + FUL + GEF

40

Tumor biomarker analysis pre- and post-treatment

00206414

MBC

II RCT

TAM +/-GEF

274

Correlate RR to HER2/A1B1 status and other biomarker studies

00069290

MBC

II RCT

ANA+/- GEF

174

biomarker study

00077025

MBC

II RCT

ANA +/- GEF

108

None specified

00066378

MBC

II

FUL+GEF

60

None specified

00234403

MBC

II RT

ANA+GEF vs FUL+GEF

148

Identify biologic predictors

00057941

MBC

II

LET +ERL

150

Correlation of EGFR, HER2 and pERSer118 to benefit

00179296

MBC: TAM resistant

II RT

GEF+/-TAM

46

Correlate early changes on PET and in plasma DNA to response

00080743

With Trastuzumab

HER2+ MBC: AI-resistant

II

TRAS monotherapy until PD followed by TRAS + LET

40

Correlate benefit with HER2 ECD at baseline and after treatment

00238290

HER2+ MBC

III RCT

ANA+/- TRAS

NA

None specified

00022672

HER2+ MBC: TRAS-naive

IV

LET+ TRAS

370

None specified

00171847

With Lapatinib (LAP)

MBC: TAM-resistant

II

LAP+TAM

41

None specified

00118157

MBC

III RCT

LET +/- LAP

128

Biomarker and genetic variant analysis

00073528

MBC: HER2 1+, 2+, 3+ or FISH+

III RCT

FUL+/-LAP

324

None specified

00390455

With FTIs: lonafarnib (LON) and tipifarnib (TIP)

MBC

II RCT

ANA +/-LON

124

None specified

00081510

MBC

II RCT

ANA +/- LON

110

None specified

00098904

MBC

II RCT

LET+ TIP (continuous) vs LET + TIP (intermittent) vs LET

108

None specified

00061971

MBC

II

TAM + TIP

27–40

Note: efficacy stratified according to benefit from prior hormone tx

00052728

MBC

II

FUL + TIP

45

Efficacy and toxicity

00082810

With mTOR inhibitors: everolimus (EVE) and temsirolimus (TEM)

Neoadjuvant PBC

II RCT

LET+/-EVE

255

None specified

00107016

MBC

II RCT

LET+/-TEM

90

None specified

00061971

With angiogenesis inhibitors: Bevacizumab (BEV), vatalanib (VAT)

Neoadjuvant PBC

II

LET+BEV

25

None specified

00161291

MBC: With acquired endocrine resistance*

II

BEV will be added to current endocrine therapy

30

Correlate metabolic response by PET to clinical benefit

00240071

MBC

II

BEV+LET

42

Tumor biomarker analysis Correlate serial endothelial and epithelial cell measurements to response and markers of angiogenesis

00187694

MBC

II

BEV+ANA or FUL

80

None specified

00405938

MBC

II

VAT+LET

32

None specified

00263198

With multitargeted TKIs: sorafenib (SOR), imatinib (IMA)

MBC: AI-resistant

I/II

ANA +SOR

50

Assess changes in Raf and VEGF signalling in tumor and stroma

00217399

MBC: PDGFR or c-kit + only

II

LET+IMA

45

Serum measurements of VEGF, bFGF, IL8, PDGF, TNF, E-selectin

00338728

Combination with HDAC inhibitor SAHA

MBC

II

TAM+SAHA

42

Pre-and post treatment ER expression and histone acetylation

00365599

*Acquired endocrine resistance defined as: actively progressing on current endocrine therapy AND history of prior response to current endocrine therapy (i.e. CR, PR or SD > 6 months). PBC, primary breast cancer; MBC, metastatic breast cancer; RCT, randomized controlled trial; RT, randomized trial; PR, partial response; SD, stable disease; ORR, objective response rate (PR+CR); ANA, anastrozole; FUL, fulvestrant; LET, letrozole; PFS, progression free survival; OS, overall survival; TAM, tamoxifen. Source: http://www.cancer.gov/clinicaltrials webcite.

Leary et al. Breast Cancer Research 2007 9:112   doi:10.1186/bcr1763