melanoma

systematic review meta-analysis network meta-analysis

Select B-Raf enzyme inhibitorscombined BRAF-MEK inhibitorsMEK inhibitorimmune checkpoint inhibitioninterferonchemotherapyAll mechanismA EFFACERMiscellaneous adjuvant settingAll type of patientFirst linesecond line (or later)       anti-CTLA-4anti-PD-1BRAF inhibitorcombined BRAF and MEK inhibitioncombined BRAF-MEK inhibitorsinterferonMEK1/2 inhibitor encorafenib plus binimetinibInterferon alphaselumetinibtrametinib + dabrafenib vemurafenibvemurafenib and cobimetinibipilimumabnivolumabpembrolizumab vs 1L unresectablevs anti-CTLA-4vs anti-PD-1vs chemotherapyvs gp100vs ipilimumabvs placebo or control       1st line2nd lineadjuvant

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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	progression or death (progression free survival PFS) (92)death (overall survival) (67)Grade 3–5 drug-related AEs (28)distant metastasis free survival (22)recurrence free survival (16)vitiligo any grade (15)vitiligo grade 3-4 (15)Adverse events leading to treatment discontinuation (12)aaa (7)objective response (ORR) (4)serious drug-related adverse events (2) Options Numeric bar chart forest plot medians
Trial	Studied trt	Control trt	patients	tags	ROB	Trial result	progression or death (progression free survival PFS)	death (overall survival)
A EFFACER
Interferon alpha
Nordic IFN Trial, 2011	ID IFN alpha-2b (I M)	observation	adjuvant			suggesting
EORTC18952 (Eggermont), 2005	ID IFN alpha-2b (I M)	observation	adjuvant			negative
EORTC18991 (Eggermont), 2008	PEG IFN alpha-2b (I M)	observation	adjuvant			suggesting
EORTC18871/DKG 80-1 (Kleeberg), 2004	rIFN alpha-2b	observation	adjuvant			negative
ipilimumab
EORTC 18071 (Eggermont), 2015        NCT	ipilimumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
nivolumab
CheckMate 238, 2017      NCT	nivolumab	ipilimumab	adjuvant	adjuvant	Low risk of bias	conclusive
pembrolizumab
KEYNOTE-054, 2018      NCT	pembrolizumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
trametinib + dabrafenib
COMBI-AD, 2017      NCT	trametinib and dabrafenib	placebo	adjuvant		Low risk of bias	suggesting
COMBI neo, 2018      NCT	trametinib and dabrafenib	SOC	adjuvant			-
vemurafenib
BRIM 8, 2018      NCT	vemurafenib	placebo	adjuvant			suggesting
All mechanism
Interferon alpha
Nordic IFN Trial, 2011	ID IFN alpha-2b (I M)	observation	adjuvant			suggesting
EORTC18952 (Eggermont), 2005	ID IFN alpha-2b (I M)	observation	adjuvant			negative
EORTC18991 (Eggermont), 2008	PEG IFN alpha-2b (I M)	observation	adjuvant			suggesting
EORTC18871/DKG 80-1 (Kleeberg), 2004	rIFN alpha-2b	observation	adjuvant			negative
ipilimumab
EORTC 18071 (Eggermont), 2015        NCT	ipilimumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
nivolumab
CheckMate 238, 2017      NCT	nivolumab	ipilimumab	adjuvant	adjuvant	Low risk of bias	conclusive
pembrolizumab
KEYNOTE-054, 2018      NCT	pembrolizumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
trametinib + dabrafenib
COMBI-AD, 2017      NCT	trametinib and dabrafenib	placebo	adjuvant		Low risk of bias	suggesting
COMBI neo, 2018      NCT	trametinib and dabrafenib	SOC	adjuvant			-
vemurafenib
BRIM 8, 2018      NCT	vemurafenib	placebo	adjuvant			suggesting
B-Raf enzyme inhibitors
encorafenib plus binimetinib
COLUMBUS, 2018      NCT	encorafenib plus binimetinib	vemurafenib	1L		Risk of bias	suggesting
trametinib + dabrafenib
COMBI-D (Long), 2014        NCT	trametinib and dabrafenib	dabrafenib	1L unresectable			suggesting
Flaherty, 2012      NCT	trametinib and dabrafenib	dabrafenib				suggesting
COMBI-AD, 2017      NCT	trametinib and dabrafenib	placebo	adjuvant		Low risk of bias	suggesting
COMBI neo, 2018      NCT	trametinib and dabrafenib	SOC	adjuvant			-
COMBI-V (Robert), 2015      NCT	trametinib and dabrafenib	vemurafenib	1L			suggesting
vemurafenib
BRIM 8, 2018      NCT	vemurafenib	placebo	adjuvant			suggesting
vemurafenib and cobimetinib
Larkin, 2014      NCT	vemurafenib and cobimetinib	vemurafenib				suggesting
combined BRAF-MEK inhibitors
encorafenib plus binimetinib
COLUMBUS, 2018      NCT	encorafenib plus binimetinib	vemurafenib	1L		Risk of bias	suggesting
trametinib + dabrafenib
Flaherty, 2012      NCT	trametinib and dabrafenib	dabrafenib				suggesting
COMBI-D (Long), 2014        NCT	trametinib and dabrafenib	dabrafenib	1L unresectable			suggesting
COMBI-AD, 2017      NCT	trametinib and dabrafenib	placebo	adjuvant		Low risk of bias	suggesting
COMBI neo, 2018      NCT	trametinib and dabrafenib	SOC	adjuvant			-
COMBI-V (Robert), 2015      NCT	trametinib and dabrafenib	vemurafenib	1L			suggesting
vemurafenib and cobimetinib
Larkin, 2014      NCT	vemurafenib and cobimetinib	vemurafenib				suggesting
immune checkpoint inhibition
ipilimumab
Robert, 2011      NCT	ipilimumab + dacarbazine	dacarbazine	1L	1st line	Low risk of bias	conclusive
Hodi (ipi + gp100), 2010      NCT	ipi + gp100	gp100	2L	2nd line	Risk of bias	suggesting
Hodi (ipi alone), 2010      NCT	ipilimumab 3 mg/kg	gp100	2L	2nd line	Risk of bias	suggesting
EORTC 18071 (Eggermont), 2015        NCT	ipilimumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
nivolumab
CheckMate 037 (Weber), 2015      NCT	nivolumab	chemotherapy	2L, anti-CTLA-4 failure	2nd line	Risk of bias	suggesting
CheckMate 066 (Robert), 2015      NCT	nivolumab	dacarbazine	1L	1st line	Low risk of bias	conclusive
CheckMate 238, 2017      NCT	nivolumab	ipilimumab	adjuvant	adjuvant	Low risk of bias	conclusive
CheckMate 067 (nivo vs ipi), 2015      NCT	nivolumab	ipilimumab	1L	1st line	Low risk of bias	conclusive
CheckMate 067 (nivo + ipi vs ipi), 2015    NCT	nivolumab + ipilimumab	ipilimumab	1L	1st line	Low risk of bias	conclusive
Postow, 2015      NCT	nivolumab + ipilimumab	ipilimumab	1L	1st line	Exploratory	-
CheckMate 067 (nivo + ipi vs nivo), 2015      NCT	nivolumab + ipilimumab	nivolumab	1L	1st line	Exploratory	-
pembrolizumab
KEYNOTE 002 (10mg/kg Q3W), 2015      NCT	pembrolizumab 10mg/kg	chemotherapy	2L	2nd line	Exploratory	suggesting
KEYNOTE 002 (2mg/kg Q3W), 2015      NCT	pembrolizumab 2mg/kg	chemotherapy	2L	2nd line	Exploratory	suggesting
KEYNOTE-006 (every 2W), 2015      NCT	pembrolizumab (every 2W)	ipilimumab	1L	1st line	Risk of bias	suggesting
KEYNOTE-006 (every 3W), 2015      NCT	pembrolizumab (every 3W)	ipilimumab	1L	1st line	Risk of bias	suggesting
KEYNOTE-001, 2014      NCT	pembrolizumab 2mg/kg	pembrolizumab 10mg/kg	2L	2nd line	Exploratory	negative
KEYNOTE-054, 2018      NCT	pembrolizumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
interferon
Interferon alpha
EORTC18952 (Eggermont), 2005	ID IFN alpha-2b (I M)	observation	adjuvant			negative
Nordic IFN Trial, 2011	ID IFN alpha-2b (I M)	observation	adjuvant			suggesting
EORTC18991 (Eggermont), 2008	PEG IFN alpha-2b (I M)	observation	adjuvant			suggesting
EORTC18871/DKG 80-1 (Kleeberg), 2004	rIFN alpha-2b	observation	adjuvant			negative
MEK inhibitor
encorafenib plus binimetinib
COLUMBUS, 2018      NCT	encorafenib plus binimetinib	vemurafenib	1L		Risk of bias	suggesting
selumetinib
Kirkwood, 2012	selumetinib	temozolomide				-
Kirkwood	selumetinib	temozolomide				-
trametinib + dabrafenib
Flaherty, 2012      NCT	trametinib and dabrafenib	dabrafenib				suggesting
COMBI-D (Long), 2014        NCT	trametinib and dabrafenib	dabrafenib	1L unresectable			suggesting
COMBI-AD, 2017      NCT	trametinib and dabrafenib	placebo	adjuvant		Low risk of bias	suggesting
COMBI neo, 2018      NCT	trametinib and dabrafenib	SOC	adjuvant			-
COMBI-V (Robert), 2015      NCT	trametinib and dabrafenib	vemurafenib	1L			suggesting
vemurafenib and cobimetinib
Larkin, 2014      NCT	vemurafenib and cobimetinib	vemurafenib				suggesting
Miscellaneous
Interferon alpha
EORTC18991 (Eggermont), 2008	PEG IFN alpha-2b (I M)	observation	adjuvant			suggesting
EORTC18871/DKG 80-1 stage III	rIFN alpha-2b	observation				-
ipilimumab
EORTC 18071 (Eggermont), 2015        NCT	ipilimumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
nivolumab
CheckMate 238 subgroup IIIB-C	nivolumab	ipilimumab				suggesting
pembrolizumab
KEYNOTE-054, 2018      NCT	pembrolizumab	placebo	adjuvant	adjuvant	Low risk of bias	conclusive
trametinib + dabrafenib
COMBI-AD, 2017      NCT	trametinib and dabrafenib	placebo	adjuvant		Low risk of bias	suggesting
vemurafenib
BRIM 8 (cohort IIIC)	vemurafenib	placebo				negative