advanced breast cancer (metastatic) clinical trials results

adrenal versus A/FCP
Rosner, 1974

versus
adrenal/oophorectomy versus FAC
Tashiro, 1990

versus
alternating versus successive
Mauriac, 1986

versus
aminoglutethimide versus hydrocortisone
Mercer, 1993

versus
second-line hormone treatment of advanced breast cancer
aminoglutethimide versus medroxyprogesterone acetate
Canney, 1988
aminoglutethimide
versus
high-dose medroxyprogesterone acetate (MPA)
postmenopausal patients with advanced breast carcinoma
Garcia-Giralt, 1992

versus
and third line hormonotherapy in advanced post-menopausal breast cancerpatients who have become resistant to tamoxifen
Samonis, 1994

versus
women with metastatic breast cancer
aminoglutethimide versus megestrol acetate
Lundgren, 1989
aminoglutethimide
versus
second-line treatment in patients with metastatic breast cancer
Russell, 1997

versus
second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer:
aminoglutethimide versus tamoxifen
Alonso-Munoz, 1988

versus
advanced postmenopausal breast cancer
Gale, 1994

versus
postmenopausal women with advanced breast cancer
aminoglutethimide + tamoxifen versus tamoxifen
Ingle, 1986
tamoxifen alone
versus
TAM plus aminoglutethimide (AG) and hydrocortisone (HC).
Rose, 1986

versus
postmenopausal patients with advanced breast cancer
anastrozole versus fulvestrant
Mauriac, 2003

versus
anastrozole versus megestrol acetate
Buzdar a, 1996

versus
postmenopausal patients with advanced breast cancer
anastrozole versus tamoxifen
TARGET (Bonneterre), 2001
anastrozole 1 mg once daily
versus
tamoxifen 20 mg once daily
first-line therapy for advanced breast cancer in 353 postmenopausal women
Milla-Santos, 2003

versus
-line therapy in postmenopausal, hormone-dependent, advanced breast cancer
androgen versus 5-fluorouracil
Goldenberg, 1975

versus
bevacizumab + capecitabine versus capecitabine
AVF2119g (Miller) cape, 2005
capecitabine + bevacizumab 15 mg/kg iv every 3 weeks
versus
capecitabine (2,500 mg/m2/d) twice daily on day 1 through 14 every 3 weeks
patients with metastatic breast cancer previously treated with an anthracycline and a taxaneopen
US
RIBBON-I (Robert) on top capecitabine, 2009
Capecitabine + bevacizumab 15 mg/kg iv every 3 weeks
versus
capecitabine (Cape; 2,000 mg/m(2) for 14 days),
irst-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancerdouble-blind
bevacizumab + docetaxel versus docetaxel
AVADO (Miles) 7.5mg, 2010
bevacizumab 7.5mg/kg every 3 weeks plus docetaxel
versus
placebo plus docetaxel
first-line treatment of HER2-negative metastatic breast cancer double-blind
AVADO (Miles) 15mg , 2009
Docetaxel + bevacizumab 7.5 mg/kg iv every 3 weeks
versus
first-line treatment of HER2-negative metastatic breast cancer
bevacizumab + endocrine therapy versus endocrine therapy
LEA,
bevacizumab + letrozole/fulvestrant
versus
letrozole or fulvestrant
first-line therapy in postmenopausal patients with human epidermal growth factor receptor 2 (HER2) -negative and hormone receptor-positive advanced breast cancer
bevacizumab + methotrexate versus methotrexate
Burstein, 2005
Methotrexate + cyclophosphamide + bevacizumab 10 mg/kg iv every 2 weeks
versus
bevacizumab + paclitaxel versus paclitaxel
Martin bevacizumab, 2011
bevacizumab 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle
versus
control
patients with HER2-negative locally recurrent or metastatic breast canceropen design
bevacizumab + taxanes versus taxanes
E2100 (Miller), 2007
NCT00028990
paclitaxel + bevacizumab 10 mg/kg iv every 2 weeks
versus
paclitaxel 90 mg per square meter of body-surface area on days 1, 8, and 15 every 4 weeks
patients with metastatic breast cancer not previously treatedopen
RIBBON-I (Robert) on top Tax or anthra, 2009
Taxanes or anthracyclines + bevacizumab 15 mg/kg iv every 3 weeks
versus
taxane (Tax) -based (nab-paclitaxel 260 mg/m(2), docetaxel 75 or 100 mg/m(2)), or anthracycline (Anthra) -based (doxorubicin or epirubicin combinations [doxorubicin/cyclophosphamide, epirubicin/cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide, o
irst-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer
bevacizumav + CT versus CT alone
RIBBON-2 (Brufsky), 2009
addition of BV to chemotherapies used as second-line treatment for MBC
versus
chemo+placebo
second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast canceropen
19 countries
CAF versus CMFVP
Smalley, 1983
cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF)
versus
cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP)
CAF alone versus MPA alone
Abe, 1995
cyclophosphamide, adriamycin, and 5-fluorouracil (CAF)
versus
CAP versus CFP
Creagan ET, 1984
four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP)
versus
CAP versus CMFVP
Kolaric, 1985

versus
CAP versus FAC
Kolaric, 1989

versus
capecitabine versus CMF
Oshaughnessy, 2001
intermittent oral capecitabine 1,255 mg/m2 twice daily (two weeks' treatment followed by a one-week rest period)
versus
intravenous CMF (cyclophosphamide. methotrexate, 5-fluorouracil [5-FU]) administered every three weeks
-line therapy for advanced/metastatic breast cancer
capecitabine versus control
Joensuu, 2009
NCT00114816
three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine
versus
three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil
women with axillary node-positive or high-risk node-negative breast cancer open-label
capecitabine versus cyclophosphamide, methotrexate, and 5-fluorouracil
Stockler, 2011

versus
capecitabine versus docetaxel + epirubicin
Mavroudis, 2010
docetaxel 75 mg/m(2) on day 1 plus capecitabine 950 mg/m(2) orally twice daily on days 1-14 (DC) in 21-day cycles
versus
docetaxel 75 mg/m(2) plus epirubicin 75 mg/m(2) (DE) on day 1
women with advanced breast cancer
capecitabine versus paclitaxel
Talbot, 2002
intermittent oral capecitabine (1255 mg m(-2) twice daily, days 1-14, (22 patients))
versus
i.v. paclitaxel (175 mg m(-2),
patients with metastatic/advanced breast cancer pretreated with anthracyclines
Moiseenko, 2000

versus
capecitabine versus pegylated liposomal doxorubicin
Jäger, 2010

versus
capecitabine versus vinorelbine
EORTC 10001 (Pajk), 2008
capecitabine 1250 mg/m(2) orally bid days 1-14
versus
vinorelbine 30 mg/m(2) i.v. days 1 and 8, both given every 3 weeks
patients with anthracycline- and taxane-pretreated metastatic breast cancer
capecitabine docetaxel versus docetaxel
GeparQuattro, 2010
NCT00288002

versus
Patients with large operable or locally advanced tumors, with hormone receptor-negative tumors, or with receptor-positive tumors but also clinically node-positive disease
capecitabine MPA versus IV CT
Hori, 0
capecitabine, + medroxyprogesterone acetate (MPA) + cyclophosphamide
versus
5-fluorouracil + adriamycin + CPA) plus MPA
metastatic breast cancer
capecitabine + docetaxel versus docetaxel alone
Verma, 2005
21-day cycles of oral capecitabine 1250 mg/m2 twice daily, on Days 1-14, plus docetaxel 75 mg/m2 Day 1
versus
docetaxel 100 mg/m2 on Day 1
patients with anthracycline-pretreated metastatic breast carcinoma
Miles, 2004

versus
patients with anthracycline-pretreated advanced/metastatic breast cancer
O'Shaughnessy, 2002
21-day cycles of oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2) on day 1
versus
docetaxel 100 mg/m(2) on day 1
patients with advanced breast cancer
capecitabine + docetaxel versus doxorubicin + cyclophosphamide
Lee, 2008

versus
women with axillary node positive, stage II/III breast cancer
carboplatin followed by CAF versus CAF
Costanza, 1999
carboplatin followed by CAF
versus
immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF)
women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease
cediranib + fulvestrant versus fulvestrant
Hyams,
NCT00454805

versus
cisplatin + epirubicin versus lonidamine + epirubicin
Berruti A, 2002
cisplatin + epirubicin
versus
lonidamine + epirubicin
Berruti B, 2002

versus
cisplatin + etoposide versus CMF
Cocconi, 1991
cisplatin (P) and etoposide (E)
versus
standard cyclophosphamide, methotrexate, and fluorouracil (CMF)
CMF + tamoxifen versus tamoxifen alone
Bezwoda, 1982
cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)
versus
CMF, cisplatin, etoposide, and doxorubicin versus CMF
Cocconi, 1999
The same single agents (C, M, F, cisplatin, etoposide, and doxorubicin) were administered in both experimental arms, but following a different policy.
versus
cyclophosphamide, methotrexate, and 5-fluorouracil
CNF versus CAF
Stewart, 1997
CNF intravenous cyclophosphamide 500 mg/m2 plus fluorouracil 500 mg/m2 + mitoxantrone 10 mg/m2 every 3 weeks
versus
CAF intravenous cyclophosphamide 500 mg/m2 plus fluorouracil 500 mg/m2 + doxorubicin (Adriamycin) 50 mg/m2 every 3 weeks
advanced breast canceropen
combination versus sequential
ANZBCTG, 1986

versus
combination of hormone therapies versus tamoxifen
Powles, 1984
combination of hormone therapies using tamoxifen, aminoglutethimide with hydrocortisone, and danazol (TAD)
versus
tamoxifen
continuous versus intermittent
Coates, 1987
continuous chemotherapy, administered until disease progression was evident
versus
intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression
Continuous AC or CMF versus Intermittent AC or CMF
Coates,

versus
Continuous chemotherapy versus Intermittent chemotherapy
Harris,

versus
CT + endocrine therapy versus endocrine therapy alone
Kiang, 1985
estrogen therapy combined with chemotherapy
versus
estrogen therapy alone
postmenopausal women with advanced breast cancer, whose tumors were rich in estrogen receptors or of unknown estrogen-receptor status
CT + oophorectomy versus oophorectomy
Ahmann, 1982
5-flourouracil, cytoxan and prednisone
versus
premenopausal patients with recurrent or advanced breast cancer
Rossof, 1982
cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) combination
versus
observation alone
Premenopausal patients with progressive measurable metastatic breast cancer who demonstrated either stable or responsive disease 12 weeks following oophorectomy
docetaxel versus doxorubicin
303 Study Group, 1999
intravenous infusion of docetaxel 100 mg/m(2) every 3 weeks for a maximum of seven treatment cycles.
versus
intravenous infusion of doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles.
patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy
docetaxel versus doxorubicin + cyclophosphamide
JCOG, 2005

versus
first-line chemotherapy in metastatic breast cancer
docetaxel versus fluorouracil, vinorelbine
TXT Group, 2002
docetaxel (100 mg m(-2)) every 3 weeks
versus
5-fluorouracil+vinorelbine: 5-fluorouracil (750 mg m(-2) per day continuous infusion) D1-5 plus vinorelbine (25 mg m(-2)) D1 and D5 of each 3-week cycle
patients with metastatic breast cancer after failure of neo/adjuvant or one line of palliative anthracycline-based chemotherapy
docetaxel versus mitomycin, vinblastine
304 Study Group, 1999
docetaxel 100 mg/m2 intravenously (i.v.) every 3 weeks
versus
mitomycin 12 mg/m2 i.v. every 6 weeks plus vinblastine 6 mg/m2 i.v. every 3 weeks
patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapyopen-label
docetaxel versus sequential methotrexate and 5-fluorouracil
Sjostrom, 1999
Docetaxel at a dose of 100 mg/m2 every 3 weeks
versus
sequential methotrexate and 5-fluorouracil
patients with advanced breast cancer who had failed previous anthracycline treatment
docetaxel versus vinorelbine
Meier, 2008
weekly docetaxel (DOC), 6 weekly doses per 8-week cycle
versus
Weekly vinorelbine
after failing anthracycline treatment
docetaxel + doxorubicin versus doxorobicin + cyclophosphamide
306 Study Group, 2003
doxorubicin 50 mg/m(2) plus docetaxel 75 mg/m(2)
versus
doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2)
first-line chemotherapy for metastatic breast cancer
docetaxel + doxorubicin versus fluorouracil, doxorubicin, cyclophosphamide
Bontenbal, 2005
AT (doxorubicin 50 mg/m(2) and docetaxel 75 mg/m2)
versus
FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2);
first-line chemotherapy in patients with metastatic breast cancer:
docetaxel + epirubicin versus epirubicin, cyclophosphamide
Blohmer, 2010
ED (epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2))
versus
EC (epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)).
first-line therapy for women with metastatic breast cancer
docetaxel + epirubicin versus fluorouracil, epirubicin, cyclophosphamide
Bonneterre, 2004
docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2)
versus
5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles
docetaxel + trastuzumab versus vinorelbine, trastuzumab
HERNATA, 2011
docetaxel 100 mg/m(2) day 1
versus
vinorelbine 30 to 35 mg/m(2) on days 1 and 8
first-line therapy of metastatic or locally advanced human epidermal growth factor receptor 2-positive breast cancer
EcisF versus ECycloF
Eisen, 1998

versus
endocrine therapy versus CT
Priestman, 1978
endocrine treatment
versus
cytotoxic treatment
Entinostat + exemestane versus exemestane
ENCORE 301, 2013
NCT00676663
entinostat 5 mg once per week + exemestane 25 mg daily
versus
exemestane plus placebo
Postmenopausal women with ER+ advanced breast cancer progressing on a nonsteroidal aromatase inhibitor
enzastaurin + fulvestrant versus Fulvestrant
De Jong,

versus
EPI + CIS versus EPI
Nielsen, 2000

versus
eribulin versus capecitabine
Trial 301 (Kaufman), 2015
NCT00337103
eribulin mesylate 1.4 mg/m2 (equivalent to eribulin 1.23 mg/m2 [expressed as free base]) intravenously over 2 to 5 minutes on days 1 and 8 until disease progression, unacceptable toxicity, or patient/investigator request to discontinue
versus
capecitabine 1.25 g/m2 orally twice per day on days 1 to 14, both in 21-day cycles
patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxaneopen-label
eribulin versus ixabepilone
Vahdat, 2013
NCT00879086
eribulin mesylate (1.4 mg/m2, 2–5 min intravenous on days 1 and 8)
versus
ixabepilone (40 mg/m2, 3 h intravenous on day 1) on a 21-day cycle
patients with metastatic breast canceropen-label
eribulin versus treatment of physician
EMBRACE (Cortes), 2011
NCT00388726
eribulin mesilate (1·4 mg/m² administered intravenously during 2–5 min on days 1 and 8 of a 21-day cycle)
versus
treatment of physician’s choice
patients with metastatic breast cancer who had received between two and fi ve previous chemotherapy regimens (two or more for advanced disease), including an anthracycline and a taxane, unless contraindicated.open-label
19 countries
everolimus + exemestane versus exemestane alone
BOLERO-2, 2011
NCT00863655
everolimus and exemestane
versus
exemestane and placebo
patients with hormone-receptor-positive advanced breast cancer who had recurrence or progression while receiving previous therapy with a nonsteroidal aromatase inhibitor in the adjuvant setting or to treat advanced disease (or both). double-blind
everolimus + tamoxifen versus tamoxifen alone
TAMRAD , 2012
NCT01298713
tamoxifen 20 mg/d plus everolimus 10 mg/d
versus
tamoxifen 20 mg/d alone
postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative, AI-resistant mBCopen-label
everolimus + trastuzumab + vinorelbine versus trastuzumab + vinorelbine alone
BOLERO-3, 2014
NCT01007942
daily everolimus (5 mg/day) plus weekly trastuzumab (2 mg/kg) and vinorelbine (25 mg/m(2)) in 3-week cycles
versus
placebo plus trastuzumab plus vinorelbine,
women with HER2-positive, trastuzumab-resistant, advanced breast carcinoma who had previously received taxane therapydouble-blind
exemestane versus fulvestrant
Chia, 2008

versus
exemestane versus megestrol acetate
Kaufmann, 2000

versus
postmenopausal women with progressive advanced breast cancer who experienced failure of tamoxifen
exemestane versus tamoxifen
Paridaens, 2003
exemestane
versus
tamoxifen
first-line hormone therapy for postmenopausal women with metastatic breast cancer
FAC versus FEC
French Epirubicin Study , 1988
fluorouracil, 500 mg/m2; cyclophosphamide, 500 mg/m2; and either epirubicin
versus
doxorubicin
Italian Study, 1988
fluorouracil, epirubicin, and cyclophosphamide
versus
fluorouracil, doxorubicin, and cyclophosphamide
fadrozole versus megestrol acetate
Bezwoda, 1998

versus
Buzdar b, 1996

versus
postmenopausal patients with metastatic breast carcinoma:
Buzdar c, 1996

versus
postmenopausal patients with metastatic breast carcinoma
fadrozole versus tamoxifen
Falkson, 1996

versus
previously untreated postmenopausal patients with metastatic breast cancer
Thuerlimann, 1996

versus
postmenopausal women with advanced breast cancer
FEC x 24 + tamoxifen versus FEC x 8 + tamoxifen
Ejlertsen,
cyclophosphamide, epirubicin and 5-fluorouracil (CEF) once every 3 weeks for a maximum of 18 months
versus
identical chemotherapy for a maximum of 6 months
fluvestrant 250mg versus exemestane
9238UK/0005 (fluvestrant alone), 0
NCT00944918
fulvestrant Intramuscular injection on days 1, 15, and 29 and then once monthly until disease progression
versus
exemestane oral, once daily until disease progression.
postmenopausal locally advanced / metastatic breast cancer patients who have progressed on NSAIs double-blind
Korea
SoFEa (Johnston) fluvestrant alone, 2012
NCT00253422
fulvestrant intramuscularly (IM) on days 1, 15, and 29 and then once monthly
versus
exemestane once daily
Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-Steroidal Aromatase Inhibitors
UK
formestane versus anastrozole
Kleeberg, 1997

versus
women with advanced breast cancer
formestane versus megestrol acetate
Freue, 2000

versus
postmenopausal patients with advanced breast cancer previously treated with tamoxifen
Thuerlimann, 1997

versus
formestane versus tamoxifen
Perez Carrion, 1994

versus
fulvestrant + anastrozole versus anastrozole
GEICAM/2006-10, 3000
NCT00543127
500 mg Im Fulvestrant day 0, 250 mg days 14 and 28(charge dose); later 250 mg each 28 days during 3 years plus 1 mg oral anastrozol per day during 5 years
versus
Anastrozol 1 mg daily for 5 yeras
Postmenopausal women with hormone receptor positive and negative Her2 tumoursopen label
spain
FACT (Bergh), 2012
NCT00256698
fulvestrant 500 mg intramuscular on day 1 and 250mgon days 15 and 29 and thereafter every fourth week3 days, until proven progression or undue toxicity, in combination with anastrozole 1 mg orally per day
versus
anastrozole orally at 1 mg per day until proven progression or undue toxicity
first-line therapy for patients with receptor-positive postmenopausal breast cancer opan-label
canada
Mehta(SWOG-S0226), 2012
NCT00075764
Fulvestrant was administered intramuscularly at a dose of 500 mg on day 1 and 250 mg on days 14 and 28 and monthly thereafter.
versus
1 mg of anastrozole orally every day (group 1), with crossover to fulvestrant alone strongly encouraged if the disease progressed,
Postmenopausal women with previously untreated with hormone-receptor (HR)-positive
fulvestrant + anastrozole versus exemestane
9238UK/0005 (combination), 0
NCT00944918

versus
postmenopausal locally advanced / metastatic breast cancer patients who have progressed on NSAIsdouble-blind
Korea
SoFEa (Johnston) combination, 2012
NCT00253422
Fulvestrant With Concomitant Anastrozole
versus
Exemestane
Postmenopausal Women With ER+ve Locally Advanced/Metastatic Breast Cancer Following Progression on Non-Steroidal Aromatase Inhibitors
fulvestrant 250mg versus anastrozole
Xu et al., 2011
NCT00327769
fulvestrant 250 mg/month
versus
1 mg/day anastrozole
receptor positive postmenopausal advanced breast cancer.double-blind
china
0021 (Osborne), 2002
NCT00635713
intramuscular injection of fulvestrant 250 mg once monthly
versus
daily oral dose of anastrozole 1 mg
postmenopausal women with advanced breast cancerdouble-blind
0020 (Howell), 2002
fulvestrant 250 mg as a once-monthly (one x 5 mL) intramuscular injection
versus
oral dose of anastrozole 1 mg
open-label
fulvestrant 250mg versus exemestane
EFECT (Chia), 0
NCT00065325
Fulvestrant 500 mg (2 x 5 mL, im injections) administered as a loading dose on Day 0, followed by 250 mg (1 x 5 mL) on Day 14, Day 28 and monthly (ie, 28 ± 3 days) thereafter.
versus
Exemestane 25 mg administered once daily by mouth (po) from Day 0.
hormone receptor positive postmenopausal women with advanced breast cancerdouble-blind
fulvestrant 250mg versus tamoxifen
9238IL/0025, 0
NCT00241449
intramuscular injection 250 mg
versus
first-line treatment for postmenopausal women with advanced breast cancer.double-blind
USA
0025 (Howell), 2004
fulvestrant 250 mg, via intramuscular injection, once monthly;
versus
tamoxifen 20 mg, orally, once daily
advanced breast cancer in postmenopausal women previously untreated with endocrine therapydouble-blind
fulvestrant 500mg versus anastrozole
FIRST (Robertson), 2010
NCT00274469
500 mg intramuscular injection
versus
anastrozole 1 mg oral tablet
First Line Hormonal Treatment for Postmenopausal Women With Hormone Receptor Positive Advanced Breast Cancer
fulvestrant 500mg versus fulvestrant 250mg
D6997L00021, 3000
NCT01300351
Fulvestrant 500mg (2 syringes of Fulvestrant 250mg), Fulvestrant 500 mg i.m. every 28 (+/- 3) days plus an additional 500 mg on day 14 (+/-3) of first month only
versus
Fulvestrant 250mg (1 syringe of fulvestrant 250mg + 1 syringe matching placebo), Fulvestrant 250 mg and matching placebo i.m. every 28 (+/- 3) days plus an additional 2 placebo syringes on day 14 (+/-3) of first month only
Chinese postmenopausal women with oestrogen receptor positive advanced breast cancer who have failed a prior endocrine treatmentdouble-blind
China
CONFIRM (Di Leo), 2010
NCT00099437
fulvestrant 500 mg (500 mg intramuscularly [IM] on day 0, then 500 mg IM on days 14 and 28 and every 28 days thereafter)
versus
fulvestrant 250 mg every 28 days
women with oestrogen receptor positive advanced breast cancer who have failed on a previous endocrine treatmentdouble-blind
US
FINDER 1 (Ohno), 2010
28-day cycles of fulvestrant
versus
postmenopausal Japanese women with advanced breast cancer
FINDER 2, 2010
NCT00313170
500 mg (high dose [HD]; 500 mg/month plus 500 mg on day 14 of Month 1).
versus
fulvestrant: 250 mg/month (approved dose [AD]);
Western postmenopausal women recurring or progressing after prior endocrine therapy
gemcitabine versus epirubicin
Feher, 2005

versus
gemcitabine + docetaxel versus capecitabine + docetaxel
Seidman, 2011

versus
gemcitabine + docetaxel versus capecitabine plus docetaxel
Chan, 2009

versus
gemcitabine + docetaxel versus docetaxel
Nielsen, 2011

versus
gemcitabine + paclitaxel versus paclitaxel monotherapy
Albain, 2008

versus
gemcitabine + paclitaxel + bevacizumab versus paclitaxel + bevacizumab
Brufsky, 2011

versus
gemcitabine + vinorelbine versus vinorelbine monotherapy
Martín, 2007

versus
gemcitabine + weekly docetaxel versus weekly docetaxel
Papadimitriou, 2009

versus
gemcitabine, epirubicin, paclitaxel versus fluorouracil, epirubicin, cyclophosphamide
CECOG BM1, 2005
gemcitabine (1,000 mg/m(2), days 1 and 4), epirubicin (90 mg/m(2), day 1), and paclitaxel (175 mg/m(2), day 1)
versus
FU (500 mg/m(2), day 1), epirubicin (90 mg/m(2), day 1), and cyclophosphamide (500 mg/m(2), day 1)
first-line chemotherapy in metastatic breast cancer
high-dose chemotherapy versus conventional-dose chemotherapy
ECOG, 200
high-dose chemotherapy plus autologous hematopoietic stem-cell transplantatio
versus
Conventional-dose chemotherapy
women with metastatic breast cancer
IBDIS, 2003

versus
NCIC, 2001

versus
PEGASE 03, 2002

versus
PEGASE 04, 1999
HD-CT using the CMA regimen (Mitoxantrone, Cyclophosphamide, Melphalan)
versus
maintenance CT
Schmid, 2005
double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation
versus
standard combination therapy with doxorubicin and paclitaxel
intermittent tamoxifen versus Intermittent tamoxifen
Beex, 2006

versus
first line endocrine treatment in advanced breast
ixabepilone (on top capecitabine) versus no ixabepilone
Sparano, 2010
ixabepilone (40 mg/m(2) intravenously on day 1) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14) given every 21 days
versus
capecitabine alone (2,500 mg/m(2) on the same schedule) given every 21 days
patients with metastatic breast cancer previously treated with anthracycline and taxanes open
Thomas, 2007
ixabepilone 40 mg/m(2) intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m(2) orally on days 1 through 14 of a 21-day cycle
versus
capecitabine alone 2,500 mg/m(2) on days 1 through 14 of a 21-day cycle
patients with metastatic breast cancer progressing after anthracycline and taxane treatmentopen
lapatinib + capecitabine versus capecitabine alone
Geyer, 2006
NCT00078572
lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle
versus
monotherapy (capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle)
Women with HER2-positive, locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumabopen-label
lapatinib + letrozole versus letrozole alone
Johnston (EGF30008) , 2009
NCT00073528
daily letrozole (2.5 mg orally) plus lapatinib (1,500 mg orally)
versus
letrozole
hormone receptor-positive metastatic breast cancer double-blind
lapatinib + paclitaxel versus paclitaxel alone
Di Leo, 2008
NCT00075270
first-line therapy with paclitaxel 175 mg/m(2) every 3 weeks plus lapatinib 1,500 mg/d
versus
paclitaxel
first-line treatment for metastatic breast cancerdouble-blind
letrozole versus aminoglutethimide
Gershanovich, 1998

versus
postmenopausal women with advanced breast cancer, previously treated with anti-estrogens
letrozole versus anastrozole
Rose, 2003

versus
second-line endocrine therapy in advanced breast cancer
letrozole versus atamestane + toremifene
Goss, 2007

versus
postmenopausal women with advanced receptor-positive breast cancer
letrozole versus fadrozole
Tominaga, 2003

versus
letrozole versus megestrol acetate
Buzdar, 2001

versus
postmenopausal women with advanced breast cancer previously treated with antiestrogens
Dombernowsky, 1998

versus
patients with locally advanced, locoregionally recurrent or metastatic breast cancer
letrozole versus tamoxifen
Mourisden, 2001

versus
first-line therapy for postmenopausal women with advanced breast cancer
Letrozole plus bevacizumab versus letrozole
Dickler (CALGB 40503°, 2015

versus
loading dose regimen of tamoxifen versus conventional dosing
Spooner, 1991

versus
advanced breast cancer
locoregional treatment versus no treatment of the primary tumour
Badwe, 2015

versus
long versus short
Ejlertsen, 1993
cyclophosphamide, epirubicin and 5-fluorouracil (CEF) once every 3 weeks for a maximum of 18 months
versus
identical chemotherapy for a maximum of 6 months
French Epirubicin Study Group, 2000
11 cycles of fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 75) every 21 days;
versus
four cycles of FEC 100 then restart the same regimen at disease progression in case of prior response or stabilization
maintenance versus control
Harris, 1990
continue until disease progression
versus
stop chemotherapy
patients with advanced recurrent breast cancer treated with four courses of mitozantrone 14 mg/m2 intravenously every 3 weeks (9 weeks)
Muss, 1991
continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy)
versus
no further treatment
women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks
Gregory, 1997
up to six extra courses of chemotherapy
versus
Falkson, 1998
maintenance therapy: cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH]
versus
observation
Nooij, 2003
Continuation of CMF
versus
non-progressing metastatic breast cancer patients after induction chemotherapy (CMF)
Gennari, 2006
eight courses of maintenance paclitaxel
versus
Alba, 2010
PLD (40 mg/m(2)) every 28 days for six cycles
versus
Patients without disease progression following first-line induction chemotherapy consisting of three cycles of doxorubicin (75 mg/m(2)) followed by three cycles of docetaxel (100 mg/m(2)) both every 21 days
medroxyprogesterone acetate versus CAF
Abe, 1995

versus
medroxyprogesterone acetate versus CAF followed by CMF
Edimburg, 1979

versus
Women with local or systemic advanced breast cancer considered to be beyond control by local treatment alone
medroxyprogesterone acetate + CAF versus CAF alone
Abe, 1995

versus
Tominaga, 1994

versus
medroxyprogesterone acetate + CT versus CT alone
Gundersen, 1992

versus
megesterol acetate versus mitozantrone
Dixon, 1992

versus
patients with advanced breast cancer unresponsive to tamoxifen
modified 3-weekly intravenous CMF versus CMF
EORTC 10808 (Engelsman), 1991
modified 3-weekly intravenous CMF
versus
cyclophosphamide/methotrexate/5-fluorouracil
motesanib + paclitaxel versus paclitaxel
Martin (motesanib), 2011
NCT00356681
motesanib 125 mg orally once per da
versus
placebo
patients with untreated HER2-negative metastatic breast cancerdouble-blind
MPEPIV or MPEMi versus CMF
Cocconi G, 1996

versus
MV versus FAC/FEC
Namer, 2001
mitoxantrone+vinorelbine (MV)
versus
5-fluorouracil+cyclophosphamide+either doxorubicin or epirubicin (FAC/FEC)
nab-paclitaxel versus docetaxel
Gradishar, 2009
NCT00274456
weekly and every 3 week (q3w) nab-paclitaxel
versus
docetaxel
first-line treatment in patients with MBC
nab-paclitaxel +gencotabine versus gencitabine
Roy, 2008
NCT00110084
weekly nab (nanoparticle albumin-bound)-paclitaxel in combination with gemcitabine
versus
patients with previously untreated metastatic breast cancer
olaparib versus Physician s choice chemotherapy
OlympiAD, 2017
NCT02000622
Olaparib (Olaparib tablet 300mg bd po)
versus
Physician's choice chemotherapy (Capecitabine 2500 mg/m2 d1-14 q 21, or Vinorelbine 30 mg/m2 d1,8 q 21, or Eribulin 1.4 mg/m2 d1,8 q 21)
women with human epidermal growth factor 2 (HER2)–negative metastatic breast cancer with a germline BRCA mutation
oophorectomy + CAF versus CAF alone
Falkson, 1995

versus
pacclitaxel versus capecitabine
Talbot, 2002
i.v. paclitaxel (175 mg m(-2),
versus
3-week cycles of intermittent oral capecitabine (1255 mg m(-2) twice daily, days 1-14,
paclitaxel versus cisplatin, etoposide
TOG, 2005

versus
paclitaxel versus CMFP
ANZ TITG, 1999
paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks)
versus
standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin re
front-line therapy in untreated metastatic breast cancer
paclitaxel versus doxorubicin
ECOG E1193 (B), 2003
paclitaxel (175 mg/m(2)/24 h),
versus
doxorubicin (60 mg/m(2)),
patients with metastatic breast cancer
EORTC 10923, 2000

versus
first-line therapy of advanced breast cancer
paclitaxel versus mitomycin
Dieras, 1995
paclitaxel 175 mg/m2 given as a 3-hour infusion every 3 weeks
versus
mitomycin 12 mg/m2 given as an intravenous infusion every 6 weeks
advanced breast cancer
paclitaxel + doxorubicin versus doxorobicin + cyclophosphamide
EORTC 10961, 2002
Doxorubicin and paclitaxel
versus
doxorubicin and cyclophosphamide
first-line chemotherapy in metastatic breast cancer
paclitaxel + doxorubicin versus fluorouracil, doxorubicin, cyclophosphamide
Jassem, 2001

versus
first-line therapy for women with metastatic breast cancer
paclitaxel + epirubicin versus epirubicin, cyclophosphamide
UKCCCR AB01, 1997
EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2)
versus
EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles
first-line chemotherapy for metastatic breast cancer
palbociclib + fulvestrant versus fulvestrant alone
PALOMA 3, 2015
NCT01942135
palbociclib (125 mg per day orally for 3 weeks, followed by 1 week off) and fulvestrant (500 mg intramuscularly per standard of care every 14 days for the first three injections and then every 28 days)
versus
placebo and fulvestrant
women with HR+, HER2 negative metastatic breast cancer whose disease has progressed after prior endocrine therapydouble-blind
17 countries
palbociclib + letrozole versus letrozole alone
PALOMA 1/TRIO-18, 2015
NCT00721409
continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles
versus
continuous oral letrozole 2.5 mg daily
postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease open-label
PCb versus PE
Fountzilas, 2002

versus
pertuzumab + trastuzumab +docetaxel versus trastuzumab + docetaxel
CLEOPATRA, 2012
NCT00567190
pertuzumab plus trastuzumab plus docetaxel
versus
placebo plus trastuzumab plus docetaxel
patients with HER2-positive metastatic breast cancer double-blind
neoSphere (Group B), 2012
NCT00545688
pertuzumab and trastuzumab plus docetaxel
versus
trastuzumab plus docetaxel
women with locally advanced, inflammatory, or early HER2-positive breast cancer
ribociclib (LEE011) + letrozole versus letrozole alone
MONALEESA-2, 2016
NCT01958021
ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day)
versus
placebo + letrozole
postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced diseasedouble-blind
Follow-up duration: 18 months
29 countries
sequentially versus combination
ANZBC, 1986
treatment sequences, doxorubicin plus cyclophosphamide (AC) followed on failure by tamoxifen (TAM), and TAM followed by AC
versus
combined modality chemo-endocrine therapy (TAM plus AC).
sorafenib + capecitabine versus capecitabine alone
Baselga, 2012
- or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day
versus
capecitabine alone
HER2-negative locally advanced or metastatic breast cancerdouble-blind
sorafenib + gemcitabine or capecitabine versus gemcitabine or capecitabine alone
Schwartzberg, 2013
NCT00493636
sorafenib (400 mg, twice daily)
versus
placebo
patients with HER-2-negative advanced breast cancer that progressed during or after bevacizumabdouble-blind
sorafenib + paclitaxel versus paclitaxel alone
Gradishar, 2013
paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off) plus sorafenib (400mg, orally, twice daily)
versus
paclitaxel (90mg/m(2), weekly, intravenously, 3 weeks on/1 week off)
first-line therapy in patients with HER2-negative advanced breast cancerdouble-blind
split dose versus Every three weeks Paclitaxel
Khoo , 2006
split-dose paclitaxel or docetaxel in combination with gemcitabine
versus
Every three weeks Gemc. Paclitaxel 175 mg/m2
Metastatic patients with metastatic breast cancer (MBC) who had previously received anthracyclines
tamofixen combination versus tamofixen sequential
ANZBC, 1986

versus
tamoxifen versus bilateral oophorectomy
Ingle, 1986

versus
tamoxifen versus CMF
Taylor, 1986

versus
tamoxifen versus diethylstilbestrol
Gockerman, 1986

versus
tamoxifen versus medroxyprogesterone
Muss, 1994

versus
patients with metastatic breast cancer
tamoxifen versus medroxyprogesterone acetate
Castiglione-Gertsch, 1993

versus
van, 1986

versus
tamoxifen versus megestrol acetate
Stuart, 1996

versus
advanced and recurrent breast cancer
Gill, 1993

versus
patients with metastatic breast cancer
Ettinger, 1986

versus
advanced breast cancer
tamoxifen versus nandrolone decanoate
Kellokumpu-Lehtinen, 1987

versus
advanced breast cancer
tamoxifen versus no systemic treatment
Beelen, 2014

versus
tamoxifen versus ovarian ablation
Sawka, 1997

versus
metastatic breast cancer in premenopausal women
tamoxifen versus radiotherapy
Willsher, 1996

versus
Locally advanced breast cancer
tamoxifen versus surgical oophorectomy
Buchanan, 1986

versus
premenopausal patients with advanced breast cancer
tamoxifen + CAF versus CAF alone
CLKGB 8081 (Perry), 1987

versus
tamoxifen + CAT versus CAT
Perry, 1985

versus
tamoxifen + CMF versus CMF
Mouridsen, 1985

versus
tamoxifen + CMF versus CMF alone
Mouridsen, 1985

versus
Viladiu, 1985

versus
tamoxifen + CMFV versus CMVF alone
Boccardo, 1985

versus
tamoxifen + fluoxymesterone + CAF versus CAF
ECOG E3186 (Sledge), 2000
chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil CAF)
versus
chemohormonal therapy (CAF plus tamoxifen and fluoxymesterone)
patients with estrogen receptor (ER)-positive or ER-unknown metastatic breast cancer
tamoxifen 20 mg/day versus 40 mg/day
Takatsuka, 1989

versus
advanced breast cancer
tamoxifen and drostanolone propionate versus CMF
Clavel, 1982

versus
temsirolimus + letrozole versus letrozole alone
HORIZON, 2013
NCT00083993
oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks)
versus
letrozole/placebo
first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancerdouble-blind
toremifene versus tamoxifen
Nomura, 1993

versus
patients with advanced or recurrent breast cancerdouble-blind
Gershanovich, 1997

versus
Milla-Santos, 2001
toremifene (TOR) 60 mgs/dayly/o.r.
versus
tamoxifen (TAM) 40 mgs/dayly/o.r.
postmenopausal women with advanced breast cancer, without previous systemic therapy double-blind
Hayes, 1995
toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d
versus
tamoxifen (TAM; 20 mg/d)
postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer
Stenbygaard, 1993

versus
Pyrhonen, 1997

versus
post-menopausal patients with advanced breast cancer who have not had prior systemic therapy
trastuzumab + anastrozole versus anastrozole alone
TAnDEM (Kaufman), 2009
anastrozole (1 mg/d orally) with trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression
versus
anastrozole
postmenopausal women with human epidermal growth factor receptor 2-positive, hormone receptor-positive metastatic breast cancer
trastuzumab + capecitabine versus capecitabine alone
von Minckwitz, 2009
trastuzumab + capecitabine
versus
capecitabine alone
Patients with HER-2-positive breast cancer that progresses during treatment with trastuzumab
trastuzumab + docetaxel versus docetaxel alone
Marty, 2005
M77001

versus
patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment
trastuzumab + lapatinib versus lapatinib alone
Blackwell, 2010
lapatinib + trastuzumab
versus
lapatinib alone
women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer
trastuzumab + letrozole versus letrozole alone
Huober, 2012
letrozole plus trastuzumab
versus
letrozole alone
patients with HER2-positive, hormone-receptor-positive metastatic breast cancer
trastuzumab + paclitaxel versus paclitaxel alone
Gasparini, 2006
trastuzumab + weekly paclitaxel
versus
weekly paclitaxel
patients with advanced breast cancer overexpressing HER-2.
trastuzumab + standard chemotherapy versus standard chemotherapy alone
Slamon, 2001
standard chemotherapy plus trastuzumab
versus
standard chemotherapy alone
women with metastatic breast cancer that overexpressed HER2
trastuzumab emtansine versus lapatinib plus capecitabine
EMILIA, 2012
NCT00829166
Trastuzumab emtansine
versus
lapatinib plus capecitabine
patients with HER2-positive advanced breast cancer, who had previously been treated with trastuzumab and a taxane
trastuzumab emtansine versus usual care
TH3RESA, 2014
NCT01419197
trastuzumab emtansine
versus
physician's choice
patients with progressive HER2-positive advanced breast cancer who had received two or more HER2-directed regimens in the advanced settingopen-label
vorozole versus megestrol acetate
Goss, 1999

versus
VP-16+P versus paclitaxel
Icli, 2002

versus
VPCMF + oophorectomy versus oophorectomy
Falkson, 1979
oophorectomy + vincristine, prednisone, cyclophosphamide, methotrexate, 5-fluorouracil (VPCMF)
versus
oophorectomy followed by an observation period (Phase 1), followed by VPCMF (Phase 2)
Weekly Docetaxel versus Every three weeks Docetaxel
Rivera , 2008
Weekly Docetaxel 35–40 mg/m2
versus
Every three weeks Docetaxel 75–100 mg/m2
Metastatic patients with metastatic breast cancer open
Tabernero , 2004
Weekly Docetaxel 40 mg/m2
versus
Every three weeks Docetaxel 100 mg/m2
Metastatic
Sedky , 2002
Weekly Docetaxel 35 mg/m2
versus
Every three weeks Docetaxel 100 mg/m2
Metastatic
Willemse , 2007
Weekly Docetaxel 36 mg/m2
versus
Every three weeks Docetaxel 100 mg/m2
Metastatic
Weekly Paclitaxel versus Every three weeks Docetaxel
Gradishar , 2009
Weekly Nab-paclitaxel 100 mg/m2
versus
Every three weeks Docetaxel 100 mg/m2
Metastatic
Fountzilas , 2008
Weekly Paclitaxel 80 mg/m2
versus
Every three weeks Gemc. Docetaxel 75 mg/m2
Metastatic
Weekly Paclitaxel versus Every three weeks Paclitaxel
CLGB 9840 (Seidman), 2008
Weekly Paclitaxel 80 mg/m2
versus
Every three weeks Paclitaxel 175 mg/m2
Metastatic
Frasci , 2006
Weekly Epi CDDP Paclitaxel 120 mg/m2
versus
Every three weeks Epi Paclitaxel 175 mg/m2
LABC
Frasci , 2005
Weekly Epi CDDP Paclitaxel 120 mg/m2
versus
Every three weeks Epi Paclitaxel 175 mg/m2
Metastatic
Sikov , 2002
Weekly Paclitaxel 150 mg/m2
versus
Split D1,8 every three weeks Paclitaxel 175 mg/m2
Metastatic