advanced breast cancer (metastatic)

systematic review meta-analysis network meta-analysis

Select AKT Inhibitorsangiogenesis inhibitorsCDK (cyclin-dependent kinase) inhibitorFGFR inhibitorsHER2 inhibitorshistone deacetylase (HDAC) inhibitorsmTOR inhibitor multi target TKIPhosphoinositide 3-kinase inhibitorpoly ADP-ribose polymerase (PARP) inhibitorlocoregional treatment of the primary tumorimmune checkpoint inhibition selective estrogen receptor modulator (SERM)aromatase inhibitorsLHRH agonistSelective estrogen receptor downregulators (SERDs)Anthracyclines based regimenCapecitabine containing-regimencombination chemotherapy with platinum saltsGemcitabine containg regimenhigh dose chemotherapyixabepilone based chemotherapymaintenance chemotherapynontaxane microtubule dynamics inhibitor TaxanesVinorelbine containing regimenmonoclonal antibody All type of patientBRCA-mutatedHER 2 negative patientsHER2 positiveHR+ HER2 -uncoded clinical condition ***       A CLASSERadd-on to anti HER-2 agentAI aloneanti PD1capecitabine containing regimenCDK4/6 inhibitorchemotherapy comparisoncombination including AIcombination with CTcombination with CT (without taxanes)combination with endocrine therapycombination with ETcombination with taxanescontinuous vs intermittentendocrine therapyendocrine therapy + CTepothilonesfulvestrant + anastrozolefulvestrant alonefulvestrant high dose alonegemcitabine regimenHDAC inhibitorshigh-dose chemotherapyinitial chemotherapylocoregional treatmentlongmaintenance CTmore cycles of chemotherapynab-paclitaxelnontaxane microtubule dynamics inhibitorpertuzumabplatin containing CTpoly ADP-ribose polymerase (PARP) inhibitorprogestogensSelective estrogen receptor modulators (SERMs)selective PI3K inhibitorsex steroid hormonestaxanes alonetaxanes in combinationtrastuzumabtrastuzumab emtansinevinorelbineweekly taxanes abemaciclib alpelisibceritinibmotesanib ribociclib taselisibaminoglutethimide anastrozolebevacizumabcapecitabine cisplatin docetaxelentinostat eribulineverolimusexemestane fadrozole formestane fulvestrant gemcitabineixabepilone lapatinib letrozolemedroxyprogesterone nab-paclitaxelniraparib olaparibpaclitaxelpalbociclib pertuzumabsorafenibtalazoparib tamoxifentemsirolimus toremifene trastuzumabtrastuzumab emtansine veliparib vinorelbine vs A CLASSERvs anti-HER2 antibody + taxanesvs chemotherapyvs combinationvs combination chemotherapyvs conventional-dose chemotherapyvs CTvs CT alonevs different AIvs endocrine therapy alonevs estrogen receptor antagonistvs Every three weeks regimenvs no bevacizumabvs observationvs placebo or controlvs single-agent chemotherapyvs taxane containing regimenvs taxanes alonevs X       1st line2nd line2nd+ lineBRCA-mutatedErbB2 positivefirst line of endocrine therapyHER-2 negativeHER-2 positiveHR positivenot previously treated by anthracyclinensNAI failurepostmenopausalprevious anthracyclinepreviously treated by HER-2 antibodypreviously treated by taxanespreviously treated with endocrine therapytrastuzumab failure

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Group by Group by... nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition MA  in first nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in second nothing pathology treatment patient comparator classe classe comparator mechanism clinical condition  in third	Description Synopsis Comparison Treatments Patients Characteristics Method Risk of bias References None Tools Indexation					Results Global trial result Main results All results All result tag NCT results	death (overall survival) (83)progression or death (progression free survival PFS) (77)objective response (ORR) (57)clinical benefit (32)hot flushes (20)nausea (18)progression (Time to progression TTP) (17)rash (15)diarrhoea (10)heart failure (grade 3) (10)treatment-related deaths (10)permanent discontinuation (10)hypertension (grade 3) (10)vomiting (8)gastrointestinal perforation (grade 3) (8)bleeding (grade 3) (8)vaginal bleeding (6)thromboembolic AE (6)arthralgia (6)serious adverse events (6)Serious adverse event (3)arterial/venous thromboembolism (grade 3) (3)cardiomyopathy (grade 3) (2) Options Numeric bar chart forest plot medians
Trial	Studied trt	Control trt	patients	tags	ROB	Trial result	death (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/day	40 mg/day				-
Ingle, 1986	tamoxifen	bilateral oophorectomy				-
Perry, 1985	tamoxifen + CAT	CAT				-
Mouridsen, 1985	tamoxifen + CMF	CMF				-
Spooner, 1991	loading dose regimen of tamoxifen	conventional dosing				-
Gockerman, 1986	tamoxifen	diethylstilbestrol				-
Beex, 2006	intermittent tamoxifen	Intermittent tamoxifen				-
Muss, 1994	tamoxifen	medroxyprogesterone				-
Castiglione-Gertsch, 1993	tamoxifen	medroxyprogesterone acetate				-
van, 1986	tamoxifen	medroxyprogesterone acetate				-
Stuart, 1996	tamoxifen	megestrol acetate				-
Gill, 1993	tamoxifen	megestrol acetate				-
Ettinger, 1986	tamoxifen	megestrol acetate				-
Kellokumpu-Lehtinen, 1987	tamoxifen	nandrolone decanoate				-
Beelen, 2014	tamoxifen	no systemic treatment				-
Sawka, 1997	tamoxifen	ovarian ablation				-
Willsher, 1996	tamoxifen	radiotherapy				-
Mauriac, 1986	alternating	successive				-
Buchanan, 1986	tamoxifen	surgical oophorectomy				-
toremifene
Nomura, 1993	toremifene	tamoxifen			Low risk of bias	negative
Gershanovich, 1997	toremifene	tamoxifen				negative
Milla-Santos, 2001	toremifene	tamoxifen			Low risk of bias	negative
Hayes, 1995	toremifene	tamoxifen				negative
Stenbygaard, 1993	toremifene	tamoxifen				negative
Pyrhonen, 1997	toremifene	tamoxifen				suggesting
angiogenesis inhibitors
not classified
LEA	bevacizumab + endocrine therapy	endocrine therapy				-
De Jong	enzastaurin + fulvestrant	Fulvestrant				-
Dickler (CALGB 40503°, 2015	Letrozole plus bevacizumab	letrozole				-
bevacizumab
RIBBON-I (Robert) on top capecitabine, 2009	bevacizumab + capecitabine	capecitabine		1st line	Low risk of bias	suggesting
AVF2119g (Miller) cape, 2005	bevacizumab + capecitabine	capecitabine		2nd line	Risk of bias	suggesting
RIBBON-2 (Brufsky), 2009	bevacizumav + CT	CT alone		2nd line		suggesting
AVADO (Miles) 15mg , 2009	bevacizumab + docetaxel	docetaxel		1st line HER-2 negative		suggesting
AVADO (Miles) 7.5mg, 2010	bevacizumab + docetaxel	docetaxel		1st line HER-2 negative	Low risk of bias	negative
Burstein, 2005	bevacizumab + methotrexate	methotrexate				negative
Martin bevacizumab, 2011	bevacizumab + paclitaxel	paclitaxel		1st line HER-2 negative	Risk of bias	negative
E2100 (Miller), 2007      NCT	bevacizumab + taxanes	taxanes		1st line	Risk of bias	suggesting
RIBBON-I (Robert) on top Tax or anthra, 2009	bevacizumab + taxanes	taxanes		1st line		suggesting
ceritinib
Hyams      NCT	cediranib + fulvestrant	fulvestrant				-
motesanib
Martin (motesanib), 2011      NCT	motesanib + paclitaxel	paclitaxel		1st line HER-2 negative	Low risk of bias	-
sorafenib
Schwartzberg, 2013      NCT	sorafenib + gemcitabine or capecitabine	gemcitabine or capecitabine alone		2nd line HER-2 negative	Exploratory	suggesting
Gradishar, 2013	sorafenib + paclitaxel	paclitaxel alone		1st line HER-2 negative	Low risk of bias	negative
Anthracyclines based regimen
not classified
Stewart, 1997	CNF	CAF				-
Smalley, 1983	CAF	CMFVP				-
ANZBC, 1986	sequentially	combination				-
Namer, 2001	MV	FAC/FEC				-
French Epirubicin Study , 1988	FAC	FEC				-
Italian Study, 1988	FAC	FEC				-
Ejlertsen	FEC x 24 + tamoxifen	FEC x 8 + tamoxifen				-
aromatase inhibitors
not classified
Goss, 1999	vorozole	megestrol acetate				suggesting
Rose, 1986	aminoglutethimide + tamoxifen	tamoxifen				negative
aminoglutethimide
Mercer, 1993	aminoglutethimide	hydrocortisone				negative
Canney, 1988	aminoglutethimide	medroxyprogesterone acetate				suggesting
Garcia-Giralt, 1992	aminoglutethimide	medroxyprogesterone acetate				negative
Samonis, 1994	aminoglutethimide	medroxyprogesterone acetate				negative
Lundgren, 1989	aminoglutethimide	megestrol acetate				negative
Russell, 1997	aminoglutethimide	megestrol acetate				negative
Alonso-Munoz, 1988	aminoglutethimide	tamoxifen				negative
Gale, 1994	aminoglutethimide	tamoxifen				negative
Ingle, 1986	aminoglutethimide + tamoxifen	tamoxifen				negative
Powles, 1984	combination of hormone therapies	tamoxifen				negative
anastrozole
Mauriac, 2003	anastrozole	fulvestrant				negative
Buzdar a, 1996	anastrozole	megestrol acetate				negative
TARGET (Bonneterre), 2001	anastrozole	tamoxifen				suggesting
Milla-Santos, 2003	anastrozole	tamoxifen				negative
exemestane
Chia, 2008	exemestane	fulvestrant				negative
Kaufmann, 2000	exemestane	megestrol acetate				negative
Paridaens, 2003	exemestane	tamoxifen				negative
fadrozole
Bezwoda, 1998	fadrozole	megestrol acetate				negative
Buzdar b, 1996	fadrozole	megestrol acetate				negative
Buzdar c, 1996	fadrozole	megestrol acetate				negative
Thuerlimann, 1996	fadrozole	tamoxifen				negative
Falkson, 1996	fadrozole	tamoxifen				negative
formestane
Kleeberg, 1997	formestane	anastrozole				negative
Thuerlimann, 1997	formestane	megestrol acetate				negative
Freue, 2000	formestane	megestrol acetate				suggesting
Perez Carrion, 1994	formestane	tamoxifen				negative
letrozole
Gershanovich, 1998	letrozole	aminoglutethimide				negative
Rose, 2003	letrozole	anastrozole				negative
Goss, 2007	letrozole	atamestane + toremifene				negative
Tominaga, 2003	letrozole	fadrozole				negative
Buzdar, 2001	letrozole	megestrol acetate				suggesting
Dombernowsky, 1998	letrozole	megestrol acetate				negative
Mourisden, 2001	letrozole	tamoxifen				negative
Capecitabine containing-regimen
capecitabine
Oshaughnessy, 2001	capecitabine	CMF				-
Joensuu, 2009      NCT	capecitabine	control			Risk of bias	-
Stockler, 2011	capecitabine	cyclophosphamide, methotrexate, and 5-fluorouracil				-
GeparQuattro, 2010      NCT	capecitabine docetaxel	docetaxel				-
Mavroudis, 2010	capecitabine	docetaxel + epirubicin				-
Verma, 2005	capecitabine + docetaxel	docetaxel alone				-
Miles, 2004	capecitabine + docetaxel	docetaxel alone				-
O'Shaughnessy, 2002	capecitabine + docetaxel	docetaxel alone				-
Lee, 2008	capecitabine + docetaxel	doxorubicin + cyclophosphamide				-
Hori	capecitabine MPA	IV CT				-
Talbot, 2002	capecitabine	paclitaxel				-
Moiseenko, 2000	capecitabine	paclitaxel				-
Jäger, 2010	capecitabine	pegylated liposomal doxorubicin				-
EORTC 10001 (Pajk), 2008	capecitabine	vinorelbine				-
CDK (cyclin-dependent kinase) inhibitor
abemaciclib
MONARCH 3, 2017        NCT	Abemaciclib +nsAI	nsAI		1st line HER-2 negative HR positive postmenopausal	Low risk of bias	conclusive
palbociclib
PALOMA 3, 2015            NCT	palbociclib + fulvestrant	fulvestrant alone	2nd line	2nd line HER-2 negative HR positive	Low risk of bias	conclusive
PALOMA-2, 2016      NCT	palbociclib + letrozole	letrozole alone	first line	1st line HER-2 negative HR positive postmenopausal	Low risk of bias	conclusive
PALOMA 1/TRIO-18, 2015      NCT	palbociclib + letrozole	letrozole alone		1st line HER-2 negative HR positive postmenopausal	Exploratory	suggesting
ribociclib
MONALEESA-2, 2016        NCT	ribociclib (LEE011) + letrozole	letrozole alone	first 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 CAF	CAF				suggesting
Creagan ET, 1984	CAP	CFP				suggesting
Cocconi, 1991	cisplatin + etoposide	CMF				suggesting
Cocconi, 1999	CMF, cisplatin, etoposide, and doxorubicin	CMF				suggesting
Cocconi G, 1996	MPEPIV or MPEMi	CMF				suggesting
Kolaric, 1985	CAP	CMFVP				suggesting
Eisen, 1998	EcisF	ECycloF				negative
Nielsen, 2000	EPI + CIS	EPI				suggesting
Kolaric, 1989	CAP	FAC				suggesting
Berruti A, 2002	cisplatin + epirubicin	lonidamine + epirubicin				negative
Berruti B, 2002	cisplatin + epirubicin	lonidamine + epirubicin				suggesting
Icli, 2002	VP-16+P	paclitaxel				suggesting
Fountzilas, 2002	PCb	PE				negative
Gemcitabine containg regimen
gemcitabine
Seidman, 2011	gemcitabine + docetaxel	capecitabine + docetaxel				-
Chan, 2009	gemcitabine + docetaxel	capecitabine plus docetaxel				-
Nielsen, 2011	gemcitabine + docetaxel	docetaxel				-
Feher, 2005	gemcitabine	epirubicin				-
Brufsky, 2011	gemcitabine + paclitaxel + bevacizumab	paclitaxel + bevacizumab				-
Albain, 2008	gemcitabine + paclitaxel	paclitaxel monotherapy				-
Martín, 2007	gemcitabine + vinorelbine	vinorelbine monotherapy				-
Papadimitriou, 2009	gemcitabine + weekly docetaxel	weekly docetaxel				-
HER2 inhibitors
pertuzumab
CLEOPATRA, 2012          NCT	pertuzumab + trastuzumab +docetaxel	trastuzumab + docetaxel		1st line HER-2 positive	Low risk of bias	suggesting
neoSphere (Group B), 2012      NCT	pertuzumab + trastuzumab +docetaxel	trastuzumab + docetaxel		HER-2 positive	Exploratory	-
trastuzumab
TAnDEM (Kaufman), 2009	trastuzumab + anastrozole	anastrozole alone		HER-2 positive HR positive		-
von Minckwitz, 2009	trastuzumab + capecitabine	capecitabine alone		HER-2 positive previously treated by HER-2 antibody trastuzumab failure		-
Marty, 2005	trastuzumab + docetaxel	docetaxel alone		1st line HER-2 positive		-
Blackwell, 2010	trastuzumab + lapatinib	lapatinib alone		ErbB2 positive previously treated by HER-2 antibody trastuzumab failure		-
Huober, 2012	trastuzumab + letrozole	letrozole alone		HER-2 positive HR positive		-
Gasparini, 2006	trastuzumab + paclitaxel	paclitaxel alone		HER-2 positive		-
Slamon, 2001	trastuzumab + standard chemotherapy	standard chemotherapy alone		HER-2 positive		-
trastuzumab emtansine
EMILIA, 2012      NCT	trastuzumab emtansine	lapatinib plus capecitabine		2nd line HER-2 positive previously treated by HER-2 antibody previously treated by taxanes		suggesting
TH3RESA, 2014    NCT	trastuzumab emtansine	usual 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 chemotherapy	conventional-dose chemotherapy				negative
IBDIS, 2003	high-dose chemotherapy	conventional-dose chemotherapy				negative
NCIC, 2001	high-dose chemotherapy	conventional-dose chemotherapy				negative
PEGASE 03, 2002	high-dose chemotherapy	conventional-dose chemotherapy				negative
PEGASE 04, 1999	high-dose chemotherapy	conventional-dose chemotherapy				negative
Schmid, 2005	high-dose chemotherapy	conventional-dose chemotherapy				negative
histone deacetylase (HDAC) inhibitors
entinostat
ENCORE 301, 2013      NCT	Entinostat + exemestane	exemestane				-
immune checkpoint inhibition
not classified
IMpassion130, 2018	atezolizumab + Nab-Paclitaxel	Nab-Paclitaxel				-
ixabepilone based chemotherapy
ixabepilone
Sparano, 2010	ixabepilone (on top capecitabine)	no ixabepilone			Risk of bias	negative
Thomas, 2007	ixabepilone (on top capecitabine)	no ixabepilone			Risk of bias	suggesting
locoregional treatment of the primary tumor
not classified
Badwe, 2015	locoregional treatment	no treatment of the primary tumour				-
maintenance chemotherapy
not classified
Mayordomo, 2009						negative
Harris, 1990	maintenance	control				negative