advanced breast cancer (metastatic)

     

Select            
Trial Studied trt Control trt patientstagsROB Trial result

selective estrogen receptor modulator (SERM)

tamoxifen
Viladiu, 1985      -
Kuss, 1997     tamoxifen -
De Lena, 1990     tamoxifen -
Takatsuka, 1989     tamoxifen 20 mg/day40 mg/day -
Ingle, 1986     tamoxifenbilateral oophorectomy -
Perry, 1985     tamoxifen + CATCAT -
Mouridsen, 1985     tamoxifen + CMFCMF -
Spooner, 1991     loading dose regimen of tamoxifenconventional dosing -
Gockerman, 1986     tamoxifendiethylstilbestrol -
Beex, 2006         intermittent tamoxifenIntermittent tamoxifen -
Muss, 1994       tamoxifenmedroxyprogesterone -
Castiglione-Gertsch, 1993     tamoxifenmedroxyprogesterone acetate -
van, 1986     tamoxifenmedroxyprogesterone acetate -
Stuart, 1996     tamoxifenmegestrol acetate -
Gill, 1993     tamoxifenmegestrol acetate -
Ettinger, 1986     tamoxifenmegestrol acetate -
Kellokumpu-Lehtinen, 1987     tamoxifennandrolone decanoate -
Beelen, 2014     tamoxifenno systemic treatment -
Sawka, 1997     tamoxifenovarian ablation -
Willsher, 1996     tamoxifenradiotherapy -
Mauriac, 1986     alternatingsuccessive -
Buchanan, 1986     tamoxifensurgical oophorectomy -
toremifene
Nomura, 1993   toremifenetamoxifenLow risk of bias negative
Gershanovich, 1997   toremifenetamoxifennegative
Milla-Santos, 2001   toremifenetamoxifenLow risk of bias negative
Hayes, 1995   toremifenetamoxifennegative
Stenbygaard, 1993   toremifenetamoxifennegative
Pyrhonen, 1997   toremifenetamoxifensuggesting

angiogenesis inhibitors

not classified
LEA     bevacizumab + endocrine therapyendocrine therapy -
De Jong     enzastaurin + fulvestrantFulvestrant -
Dickler (CALGB 40503°, 2015       Letrozole plus bevacizumabletrozole -
bevacizumab
RIBBON-I (Robert) on top capecitabine, 2009     bevacizumab + capecitabinecapecitabine 1st line Low risk of bias suggesting
AVF2119g (Miller) cape, 2005   bevacizumab + capecitabinecapecitabine 2nd line Risk of bias suggesting
RIBBON-2 (Brufsky), 2009     bevacizumav + CTCT alone 2nd line suggesting
AVADO (Miles) 15mg , 2009     bevacizumab + docetaxeldocetaxel 1st line HER-2 negative suggesting
AVADO (Miles) 7.5mg, 2010   bevacizumab + docetaxeldocetaxel 1st line HER-2 negative Low risk of bias negative
Burstein, 2005   bevacizumab + methotrexatemethotrexatenegative
Martin bevacizumab, 2011     bevacizumab + paclitaxelpaclitaxel 1st line HER-2 negative Risk of bias negative
E2100 (Miller), 2007      NCTbevacizumab + taxanestaxanes 1st line Risk of bias suggesting
RIBBON-I (Robert) on top Tax or anthra, 2009     bevacizumab + taxanestaxanes 1st line suggesting
ceritinib
Hyams      NCTcediranib + fulvestrantfulvestrant -
motesanib
Martin (motesanib), 2011      NCTmotesanib + paclitaxelpaclitaxel 1st line HER-2 negative Low risk of bias -
sorafenib
Schwartzberg, 2013      NCTsorafenib + gemcitabine or capecitabinegemcitabine or capecitabine alone 2nd line HER-2 negative Exploratory suggesting
Gradishar, 2013     sorafenib + paclitaxelpaclitaxel alone 1st line HER-2 negative Low risk of bias negative

Anthracyclines based regimen

not classified
Stewart, 1997     CNFCAF -
Smalley, 1983   CAFCMFVP -
ANZBC, 1986     sequentiallycombination -
Namer, 2001     MVFAC/FEC -
French Epirubicin Study , 1988     FACFEC -
Italian Study, 1988     FACFEC -
Ejlertsen   FEC x 24 + tamoxifenFEC x 8 + tamoxifen -

aromatase inhibitors

not classified
Goss, 1999   vorozolemegestrol acetatesuggesting
Rose, 1986   aminoglutethimide + tamoxifentamoxifennegative
aminoglutethimide
Mercer, 1993   aminoglutethimidehydrocortisonenegative
Canney, 1988   aminoglutethimidemedroxyprogesterone acetatesuggesting
Garcia-Giralt, 1992   aminoglutethimidemedroxyprogesterone acetatenegative
Samonis, 1994   aminoglutethimidemedroxyprogesterone acetatenegative
Lundgren, 1989   aminoglutethimidemegestrol acetatenegative
Russell, 1997   aminoglutethimidemegestrol acetatenegative
Alonso-Munoz, 1988   aminoglutethimidetamoxifennegative
Gale, 1994   aminoglutethimidetamoxifennegative
Ingle, 1986   aminoglutethimide + tamoxifentamoxifennegative
Powles, 1984   combination of hormone therapiestamoxifennegative
anastrozole
Mauriac, 2003   anastrozolefulvestrantnegative
Buzdar a, 1996   anastrozolemegestrol acetatenegative
TARGET (Bonneterre), 2001   anastrozoletamoxifensuggesting
Milla-Santos, 2003   anastrozoletamoxifennegative
exemestane
Chia, 2008   exemestanefulvestrantnegative
Kaufmann, 2000   exemestanemegestrol acetatenegative
Paridaens, 2003   exemestanetamoxifennegative
fadrozole
Bezwoda, 1998   fadrozolemegestrol acetatenegative
Buzdar b, 1996   fadrozolemegestrol acetatenegative
Buzdar c, 1996   fadrozolemegestrol acetatenegative
Thuerlimann, 1996   fadrozoletamoxifennegative
Falkson, 1996   fadrozoletamoxifennegative
formestane
Kleeberg, 1997   formestaneanastrozolenegative
Thuerlimann, 1997   formestanemegestrol acetatenegative
Freue, 2000   formestanemegestrol acetatesuggesting
Perez Carrion, 1994   formestanetamoxifennegative
letrozole
Gershanovich, 1998   letrozoleaminoglutethimidenegative
Rose, 2003   letrozoleanastrozolenegative
Goss, 2007   letrozoleatamestane + toremifenenegative
Tominaga, 2003   letrozolefadrozolenegative
Buzdar, 2001   letrozolemegestrol acetatesuggesting
Dombernowsky, 1998   letrozolemegestrol acetatenegative
Mourisden, 2001   letrozoletamoxifennegative

Capecitabine containing-regimen

capecitabine
Oshaughnessy, 2001     capecitabineCMF -
Joensuu, 2009      NCTcapecitabinecontrolRisk of bias -
Stockler, 2011     capecitabinecyclophosphamide, methotrexate, and 5-fluorouracil -
GeparQuattro, 2010      NCTcapecitabine docetaxeldocetaxel -
Mavroudis, 2010     capecitabinedocetaxel + epirubicin -
Verma, 2005     capecitabine + docetaxeldocetaxel alone -
Miles, 2004     capecitabine + docetaxeldocetaxel alone -
O'Shaughnessy, 2002     capecitabine + docetaxeldocetaxel alone -
Lee, 2008     capecitabine + docetaxeldoxorubicin + cyclophosphamide -
Hori     capecitabine MPAIV CT -
Talbot, 2002     capecitabinepaclitaxel -
Moiseenko, 2000     capecitabinepaclitaxel -
Jäger, 2010   capecitabinepegylated liposomal doxorubicin -
EORTC 10001 (Pajk), 2008     capecitabinevinorelbine -

CDK (cyclin-dependent kinase) inhibitor

abemaciclib
MONARCH 3, 2017        NCTAbemaciclib +nsAInsAI 1st line HER-2 negative HR positive postmenopausal Low risk of bias conclusive
palbociclib
PALOMA 3, 2015            NCTpalbociclib + fulvestrantfulvestrant alone2nd line 2nd line HER-2 negative HR positive Low risk of bias conclusive
PALOMA-2, 2016      NCTpalbociclib + letrozoleletrozole alonefirst line 1st line HER-2 negative HR positive postmenopausal Low risk of bias conclusive
PALOMA 1/TRIO-18, 2015      NCTpalbociclib + letrozoleletrozole alone 1st line HER-2 negative HR positive postmenopausal Exploratory suggesting
ribociclib
MONALEESA-2, 2016        NCTribociclib (LEE011) + letrozoleletrozole alonefirst line 1st line HER-2 negative HR positive postmenopausal Low risk of bias conclusive

combination chemotherapy with platinum salts

cisplatin
Costanza, 1999   carboplatin followed by CAFCAFsuggesting
Creagan ET, 1984   CAPCFPsuggesting
Cocconi, 1991   cisplatin + etoposideCMFsuggesting
Cocconi, 1999   CMF, cisplatin, etoposide, and doxorubicinCMFsuggesting
Cocconi G, 1996   MPEPIV or MPEMiCMFsuggesting
Kolaric, 1985   CAPCMFVPsuggesting
Eisen, 1998     EcisFECycloFnegative
Nielsen, 2000   EPI + CISEPIsuggesting
Kolaric, 1989   CAPFACsuggesting
Berruti A, 2002   cisplatin + epirubicinlonidamine + epirubicinnegative
Berruti B, 2002   cisplatin + epirubicinlonidamine + epirubicinsuggesting
Icli, 2002   VP-16+Ppaclitaxelsuggesting
Fountzilas, 2002       PCbPEnegative

Gemcitabine containg regimen

gemcitabine
Seidman, 2011     gemcitabine + docetaxel capecitabine + docetaxel -
Chan, 2009     gemcitabine + docetaxelcapecitabine plus docetaxel -
Nielsen, 2011     gemcitabine + docetaxeldocetaxel -
Feher, 2005     gemcitabineepirubicin -
Brufsky, 2011     gemcitabine + paclitaxel + bevacizumabpaclitaxel + bevacizumab -
Albain, 2008     gemcitabine + paclitaxelpaclitaxel monotherapy -
Martín, 2007     gemcitabine + vinorelbinevinorelbine monotherapy -
Papadimitriou, 2009       gemcitabine + weekly docetaxelweekly docetaxel -

HER2 inhibitors

pertuzumab
CLEOPATRA, 2012          NCTpertuzumab + trastuzumab +docetaxeltrastuzumab + docetaxel 1st line HER-2 positive Low risk of bias suggesting
neoSphere (Group B), 2012      NCTpertuzumab + trastuzumab +docetaxeltrastuzumab + docetaxel HER-2 positive Exploratory -
trastuzumab
TAnDEM (Kaufman), 2009   trastuzumab + anastrozoleanastrozole alone HER-2 positive HR positive -
von Minckwitz, 2009   trastuzumab + capecitabinecapecitabine alone HER-2 positive previously treated by HER-2 antibody trastuzumab failure -
Marty, 2005   trastuzumab + docetaxeldocetaxel alone 1st line HER-2 positive -
Blackwell, 2010   trastuzumab + lapatiniblapatinib alone ErbB2 positive previously treated by HER-2 antibody trastuzumab failure -
Huober, 2012   trastuzumab + letrozoleletrozole alone HER-2 positive HR positive -
Gasparini, 2006   trastuzumab + paclitaxelpaclitaxel alone HER-2 positive -
Slamon, 2001   trastuzumab + standard chemotherapystandard chemotherapy alone HER-2 positive -
trastuzumab emtansine
EMILIA, 2012      NCTtrastuzumab emtansinelapatinib plus capecitabine 2nd line HER-2 positive previously treated by HER-2 antibody previously treated by taxanes suggesting
TH3RESA, 2014    NCTtrastuzumab emtansineusual care 2nd+ line HER-2 positive previously treated by HER-2 antibody Risk of bias suggesting

high dose chemotherapy

not classified
ECOG, 200   high-dose chemotherapyconventional-dose chemotherapynegative
IBDIS, 2003   high-dose chemotherapyconventional-dose chemotherapynegative
NCIC, 2001   high-dose chemotherapyconventional-dose chemotherapynegative
PEGASE 03, 2002   high-dose chemotherapyconventional-dose chemotherapynegative
PEGASE 04, 1999   high-dose chemotherapyconventional-dose chemotherapynegative
Schmid, 2005   high-dose chemotherapyconventional-dose chemotherapynegative

histone deacetylase (HDAC) inhibitors

entinostat
ENCORE 301, 2013      NCTEntinostat + exemestaneexemestane -

ixabepilone based chemotherapy

ixabepilone
Sparano, 2010       ixabepilone (on top capecitabine)no ixabepiloneRisk of bias negative
Thomas, 2007     ixabepilone (on top capecitabine)no ixabepiloneRisk of bias suggesting

locoregional treatment of the primary tumor

not classified
Badwe, 2015     locoregional treatmentno treatment of the primary tumour -

maintenance chemotherapy

not classified
Mayordomo, 2009   negative
Harris, 1990     maintenancecontrolnegative
Muss, 1991     maintenancecontrolnegative
Gregory, 1997     maintenancecontrolnegative
Falkson, 1998     maintenancecontrolnegative
Nooij, 2003     maintenancecontrolnegative
Gennari, 2006     maintenancecontrolnegative
Alba, 2010     maintenancecontrolnegative
Coates, 1987     continuousintermittentnegative
Ejlertsen, 1993   longshortsuggesting
French Epirubicin Study Group, 2000     longshortnegative

mTOR inhibitor

everolimus
BOLERO-2, 2011        NCTeverolimus + exemestaneexemestane alone HER-2 negative HR positive nsNAI failure previously treated with endocrine therapy Low risk of bias conclusive
TAMRAD , 2012      NCTeverolimus + tamoxifentamoxifen alone 1st line HER-2 negative HR positive postmenopausal previously treated with endocrine therapy Risk of bias suggesting
BOLERO-3, 2014      NCTeverolimus + trastuzumab + vinorelbinetrastuzumab + vinorelbine alone HER-2 positive previously treated by taxanes trastuzumab failure Low risk of bias conclusive
temsirolimus
HORIZON, 2013      NCTtemsirolimus + letrozoleletrozole alone 1st line HR positive postmenopausal Low risk of bias negative