advanced breast cancer (metastatic)

     

Select            
Trial Studied trt Control trt patientstagsROB Trial resultdeath (overall survival) progression or death (progression free survival PFS)

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 -15%-32%
AVF2119g (Miller) cape, 2005   bevacizumab + capecitabinecapecitabine 2nd line Risk of bias suggesting7%-2%
RIBBON-2 (Brufsky), 2009     bevacizumav + CTCT alone 2nd line suggesting-10%-22%
AVADO (Miles) 15mg , 2009     bevacizumab + docetaxeldocetaxel 1st line HER-2 negative suggesting-8%-31%
AVADO (Miles) 7.5mg, 2010   bevacizumab + docetaxeldocetaxel 1st line HER-2 negative Low risk of bias negative5%-14%
Burstein, 2005   bevacizumab + methotrexatemethotrexatenegative
Martin bevacizumab, 2011     bevacizumab + paclitaxelpaclitaxel 1st line HER-2 negative Risk of bias negative-21%
E2100 (Miller), 2007      NCTbevacizumab + taxanestaxanes 1st line Risk of bias suggesting-14%-44%
RIBBON-I (Robert) on top Tax or anthra, 2009     bevacizumab + taxanestaxanes 1st line suggesting 3%-23%
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 suggesting1%-36%
Gradishar, 2013     sorafenib + paclitaxelpaclitaxel alone 1st line HER-2 negative Low risk of bias negative2%-21%

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 10%27%
Rose, 1986   aminoglutethimide + tamoxifentamoxifennegative-9%
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 -11%25%
Alonso-Munoz, 1988   aminoglutethimidetamoxifennegative
Gale, 1994   aminoglutethimidetamoxifennegative 12%-16%
Ingle, 1986   aminoglutethimide + tamoxifentamoxifennegative -21%-15%
Powles, 1984   combination of hormone therapiestamoxifennegative
anastrozole
Mauriac, 2003   anastrozolefulvestrantnegative34%
Buzdar a, 1996   anastrozolemegestrol acetatenegative -22%
TARGET (Bonneterre), 2001   anastrozoletamoxifensuggesting-3%-18%
Milla-Santos, 2003   anastrozoletamoxifennegative -8%
exemestane
Chia, 2008   exemestanefulvestrantnegative4%
Kaufmann, 2000   exemestanemegestrol acetatenegative -15%-18%
Paridaens, 2003   exemestanetamoxifennegative
fadrozole
Bezwoda, 1998   fadrozolemegestrol acetatenegative35%
Buzdar b, 1996   fadrozolemegestrol acetatenegative
Buzdar c, 1996   fadrozolemegestrol acetatenegative
Thuerlimann, 1996   fadrozoletamoxifennegative-9%
Falkson, 1996   fadrozoletamoxifennegative
formestane
Kleeberg, 1997   formestaneanastrozolenegative
Thuerlimann, 1997   formestanemegestrol acetatenegative-7%
Freue, 2000   formestanemegestrol acetatesuggesting6%
Perez Carrion, 1994   formestanetamoxifennegative
letrozole
Gershanovich, 1998   letrozoleaminoglutethimidenegative-28%
Rose, 2003   letrozoleanastrozolenegative
Goss, 2007   letrozoleatamestane + toremifenenegative
Tominaga, 2003   letrozolefadrozolenegative
Buzdar, 2001   letrozolemegestrol acetatesuggesting-8%-1%
Dombernowsky, 1998   letrozolemegestrol acetatenegative-18%-2%
Mourisden, 2001   letrozoletamoxifennegative -30%

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-46%
palbociclib
PALOMA 3, 2015            NCTpalbociclib + fulvestrantfulvestrant alone2nd line 2nd line HER-2 negative HR positive Low risk of bias conclusive-58%
PALOMA-2, 2016      NCTpalbociclib + letrozoleletrozole alonefirst line 1st line HER-2 negative HR positive postmenopausal Low risk of bias conclusive-42%
PALOMA 1/TRIO-18, 2015      NCTpalbociclib + letrozoleletrozole alone 1st line HER-2 negative HR positive postmenopausal Exploratory suggesting-51%
ribociclib
MONALEESA-2, 2016        NCTribociclib (LEE011) + letrozoleletrozole alonefirst line 1st line HER-2 negative HR positive postmenopausal Low risk of bias conclusive-44%

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-32%-38%
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-32%-35%
TH3RESA, 2014    NCTtrastuzumab emtansineusual care 2nd+ line HER-2 positive previously treated by HER-2 antibody Risk of bias suggesting-47%

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 -

immune checkpoint inhibition

not classified
IMpassion130, 2018   atezolizumab + Nab-Paclitaxel Nab-Paclitaxel -

ixabepilone based chemotherapy

ixabepilone
Sparano, 2010       ixabepilone (on top capecitabine)no ixabepiloneRisk of bias negative-10%
Thomas, 2007     ixabepilone (on top capecitabine)no ixabepiloneRisk of bias suggesting-10%-25%

locoregional treatment of the primary tumor

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

maintenance chemotherapy

not classified
Mayordomo, 2009   negative-6%
Harris, 1990     maintenancecontrolnegative6%
Muss, 1991     maintenancecontrolnegative11%