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Table 1 Characteristics of randomized controlled trials included in the NMA

From: Comparative efficacy and safety of adjuvant nivolumab versus other treatments in adults with resected melanoma: a systematic literature review and network meta-analysis

Trial

Primary publication

ClinicalTrials.gov identifier

Treatment 1

Treatment 2

Treatment 3

Blinding

Phase

Multicenter

Region

Trials included in final NMAs

ECOG 1697 [22]

Agarwala et al. (2017)

NCT00003641

IFN alfa-2b (high-dose)

Observation

NA

Open-label

III

Yes

Australia, Canada, South Africa, USA

Scottish study [23]

Cameron et al. (2001)

NA

IFN alfa-2b (low-dose)

Observation

NA

Open-label

NR

Yes

Scotland

WHO Melanoma Programme Trial 16 [24]

Cascinelli et al. (2001)

NA

IFN alfa-2b (low-dose)

Observation

NA

Open-label

NR

Yes

Italy

EORTC 18071 [25]

Eggermont et al. (2015)

NCT00636168

Ipilimumab

Placebo

NA

Double-blind

III

Yes

Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Italy, Netherlands, Norway, Poland, Russia, Spain, Sweden, Switzerland, United Kingdom, USA

EORTC 18952 [26]

Eggermont et al. (2005)

NA

IFN alfa-2b (high-dose/ 13 months)

IFN alfa-2b (low-dose/ 25 months)

Observation

Open-label

III

Yes

Austria, Belgium, Bulgaria, Croatia, Estonia, Finland, France, Germany, Hungary, Israel, Italy, Poland, Portugal, Russia, Serbia and Montenegro, Slovakia, Spain, Sweden, Switzerland, Netherlands, Turkey, United Kingdom

EORTC 18991 [27]

Eggermont et al. (2008)

NCT00006249

PEG IFN alfa-2b

Observation

NA

Open-label

III

Yes

Australia, Belgium, Bulgaria, Croatia, Czech Republic, Estonia, France, Germany, Israel, Italy, Netherlands, Poland, Portugal, Slovenia, Spain, Switzerland, Turkey, United Kingdom

KEYNOTE-054 [28, 29]

Eggermont et al. (2018)

NCT02362594

Pembrolizumab

Placebo

NA

Double-blind

III

Yes

Australia, Belgium, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Serbia, Spain, Sweden, Switzerland, United Kingdom, USA

S0008 [30]

Flaherty et al. (2014)

NCT00006237

IFN alfa-2b (high-dose)

Other chemotherapy

NA

Open-label

III

Yes

Australia, USA

Garbe 2008 (DeCOG) [31]

Garbe et al. (2008)

NA

IFN alfa-2a (low-dose)

IFN alfa-2a + dacarbazine

Observation

Open-label

III

Yes

Germany, Switzerland

AIM HIGH Study [32]

Hancock et al. (2004)

NA

IFN alfa-2a (low-dose)

Observation

NA

Open-label

III

Yes

United Kingdom

Nordic IFN Trial [33]

Hansson et al. (2011)

NCT01259934

IFN alfa-2b (1 year)

IFN alfa-2b (2 years)

Observation

Open-label

III

Yes

Denmark, Finland, Norway, Sweden

Kim et al. 2009 [34]

–

NA

Cisplatin, vinblastine, dacarbazine, IFN alfa-2b, interleukin-2

IFN alfa-2b (high-dose)

IFN alfa-2b (low-dose)

Open-label

III

NR

USA

ECOG 1690 [35]

Kirkwood et al. (2000)

NA

IFN alfa-2b (low-dose)

IFN alfa-2b (high-dose)

Observation

Open-label

III

Yes

USA

ECOG 1684 [10]

Kirkwood et al. (1996)

NA

IFN alfa-2b (high-dose)

Observation

NA

Open-label

III

Yes

USA

EORTC 18871 [36]

Kleeberg et al. (2004)

NA

rIFN alfa-2b

Observation

NA

Open-label

III

Yes

Austria, Belgium, Czech Republic, Estonia, France, Germany, Great Britain, Greece, Israel, Poland, Spain, Switzerland, Yugoslavia

COMBI-AD [7, 37]

Long et al. (2017)

NCT01682083

Dabrafenib + trametinib

Placebo

NA

Double-blind

III

Yes

Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Japan, Netherlands, New Zealand, Norway, Poland, Russia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, USA

Stadler et al. (2006) [38]

–

NA

Dacarbazine + natural human IFN alfa

Observation

NA

Open-label

NR

Yes

Germany

E1609 [39]

Tarhini et al. (2017)

NCT01274338

Ipilimumab (high-dose)

Ipilimumab (low-dose)

IFN alfa-2b (high-dose)

Open-label

III

Yes

Canada, USA

CheckMate 238 [15, 40]

Weber et al. (2017)

NA

Nivolumab

Ipilimumab

NA

Double-blind

III

Yes

Argentina, Australia, Austria, Belgium, Canada, Czech Republic, Finland, France, Greece, Hungary, Ireland, Israel, Italy, Japan, Korea, Netherlands, Norway, Poland, Romania, South Africa, Spain, Sweden, Switzerland, Taiwan, United Kingdom, USA

Trials excluded from final NMAs

Eigentler et al. 2016 (DeCOG) [41]

Eigentler et al. (2016)

NCT00204529

PEG IFN alfa-2a

IFN alfa-2a (low-dose)

NA

Open-label

III

Yes

Austria, Germany

EADO study [42]

Grob et al. (2013)

NCT00221702

PEG IFN alfa-2b

IFN alfa-2b (low-dose)

NA

Open-label

III

Yes

Austria, France, Germany

Lian et al. (2013) [43]

–

NA

IFN alfa-2b (high-dose)

Chemotherapy

Observation

NR

II

No

China

Sunbelt Melanoma Trial [44]

McMasters et al. (2016)

NA

IFN alfa-2b (high-dose)

Observation

NA

Open-label

III

Yes

Canada, USA

MM-ADJ-5 [45]

Mohr et al. (2015)

NCT00226408

IFN alfa-2b (high-dose)

IFN alfa-2b (intermittent high-dose)

NA

Open-label

III

Yes

Austria, Germany, Greece, Switzerland

Tobin et al. (2018) [46]

–

NCT02403778

Ipilimumab

Ipilimumab plus ATRA

NA

Open-label

II

No

USA

Wang et al. (2015) [47]

–

NA

IFN alfa-2b (high-dose)

Observation

NA

Open-label

II

No

China

  1. ATRA all-trans retinoic acid, IFN interferon, NA not applicable, NMA network meta-analysis, NR not reported, PEG pegylated, rIFN recombinant IFN