melanoma

Description Results NMA

PFS 0.65 [0.50; 0.85]

OS 0.72 [0.49; 1.08]

PFS 0.80 [0.54; 1.18]

RFS 0.80 [0.54; 1.18]

DMFS 0.91 [0.57; 1.45]

e twice-daily adjuvant oral vemurafenib 960 mg tablets for52 weeks (13×28-day cycles) (n=-9)

vs.

placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PFS 0.54 [0.41; 0.71]

oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily (n=192)

vs.

oral vemurafenib 960 mg twice daily (n=191)

3 arms: oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily (encorafenib plus binimetinib group), oral encorafenib 300 mg once daily (encorafenib group), or oral vemurafenib 960 mg twice daily (vemurafenib group)

open label

Sample size: 192/191

Primary endpoint: Progression free survival

FU duration: 16.6 mo (median)

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

PFS 0.39 [0.25; 0.61] median 9.4 mo vs. 5.8 mo

OS 0.63 [0.42; 0.94]

PFS 0.75 [0.57; 0.99]

OS 0.69 [0.53; 0.89]

PFS 0.56 [0.46; 0.69] median 11.4 mo vs. 7.3 mo

dabrafenib (150 mg) plus trametinib (1 or 2 mg) (n=162)

vs.

dabrafenib monotherapy (n=-9)

Sample size: 162/-9

Primary endpoint:

FU duration:

phase 2

dabrafenib and trametinib (n=423)

vs.

dabrafenib monotherapy (n=0)

Sample size: 423/0

Primary endpoint: Progression-Free Survival

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

OS 0.57 [0.42; 0.78]

PFS 0.47 [0.39; 0.57]

distant metastasis free survival 0.51 [0.40; 0.65]

dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months (n=-9)

vs.

placebo (n=-9)

double-blind

Sample size: -9/-9

Primary endpoint: Relapse-free survival

FU duration:

PFS 0.51 [0.39; 0.67] median 9.9 mo vs. 6.2 mo

vemurafenib and cobimetinib (n=-9)

vs.

vemurafenib and placebo (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

OS 0.72 [0.59; 0.87] median 11.2 mo vs. 9.1 mo Demonstrated

ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) (n=-9)

vs.

dacarbazine (850 mg per square meter) (n=-9)

double blind

Parallel groups

Sample size: -9/-9

Primary endpoint: OS

FU duration:

OS 0.64 [0.49; 0.84] median 10.1 mo vs. 6.4 mo

vitiligo all grade -9.00 [NaN; NaN]

vitiligo (grade 3-4) -9.00 [NaN; NaN]

OS 0.69 [0.56; 0.85] median 10.0 mo vs. 6.4 mo

vitiligo all grade -9.00 [NaN; NaN]

vitiligo (grade 3-4) -9.00 [NaN; NaN]

ipilimumab 3mg/kg every 3 weeks up to 4 treatments (n=137)

vs.

gp100 alone (n=136)

3 arms: ipilimumab plus gp100, ipilimumab alone, or gp100 alone

open-label

Parallel groups

Sample size: 137/136

Primary endpoint: overall surviva

FU duration:

Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with gp100 every 3 weeks for up to four treatments (n=403)

vs.

gp100 alone (n=136)

3 arms: ipilimumab plus gp100, ipilimumab alone, or gp100 alone

open-label

Parallel groups

Sample size: 403/136

Primary endpoint: overall surviva

FU duration:

recurrence free survival 0.76 [0.64; 0.90] Demonstrated

OS 0.72 [0.58; 0.89]

PFS 0.76 [0.64; 0.90]

distant metastasis free survival 0.76 [0.63; 0.91]

grade 3-4 2.07 [1.74; 2.46]

ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred (n=475)

vs.

placebo (n=476)

double-blind

Parallel groups

Sample size: 475/476

Primary endpoint: RFS

FU duration: 5.3 years

phase 3

recurrence free survival 0.65 [0.51; 0.83] Demonstrated

PFS 0.65 [0.51; 0.83]

Adverse events leading to discontinuation of drug 0.23 [0.17; 0.31]

Grade 3 or 4 drug-related adverse events 0.31 [0.24; 0.40]

nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (n=453)

vs.

ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (n=453)

double-blind

Parallel groups

Sample size: 453/453

Primary endpoint: Recurrence free survival

FU duration: 18 months (median)

Nivolumab + ipilumab (n=314)

vs.

nivolumab alone (n=316)

3 arms: nivolumab alone, nivolumab combined with ipilimumab, ipilumab alone

double-blind

Parallel groups

Sample size: 314/316

Primary endpoint: PFS, OS

FU duration:

this comparison (nivo+ipi versus nivo) was not planned and could not be considered as interential

OS 0.42 [0.25; 0.71] median not reached vs. 10.8 mo Demonstrated

PFS 0.43 [0.34; 0.55] median 5.1 mo vs. 2.2 mo

Vitiligo any grade 21.89 [2.98; 160.92]

Adverse events leading to discontinuation of drug 0.58 [0.31; 1.09]

Grade 3 or 4 drug-related adverse events 0.66 [0.41; 1.07]

Vitiligo grade 3-4 NaN [NaN; NaN]

overall response rate 3.72 [1.41; 9.85]

Grade 3 or 4 drug-related adverse events 0.29 [0.18; 0.46]

nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (n=210)

vs.

dacarbazine at a dose of 1000 mg per square meter of body-surface area every 3 weeks (n=208)

double-blind

Parallel groups

Sample size: 210/208

Primary endpoint: OS

FU duration:

ntravenous infusion of nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxic eff ects (n=272)

vs.

investigator’s choice of chemotherapy (dacarbazine 1000 mg/m² every 3 weeks or paclitaxel 175 mg/m² combined with carboplatin area under the curve 6 every 3 weeks) (n=133)

open-label

Parallel groups

Sample size: 272/133

Primary endpoint: ORR, OS

FU duration:

phase 3

PFS 0.42 [0.31; 0.57] median 11.5 mo vs. 2.9 mo Demonstrated

Adverse events leading to discontinuation of drug 2.46 [1.82; 3.34]

Grade 3 or 4 drug-related adverse events 2.01 [1.63; 2.47]

PFS 0.57 [0.43; 0.76] median 6.9 mo vs. 2.9 mo Demonstrated

Adverse events leading to discontinuation of drug 0.52 [0.32; 0.83]

Grade 3 or 4 drug-related adverse events 0.60 [0.44; 0.81]

1mg of nivolumab per kilogram every 3 weeks plus 3 mg of ipilimumab per kilogram every 3 weeks for 4 doses, followed by 3 mg of nivolumab per kilogram every 2 weeks for cycle 3 and beyond (n=314)

vs.

3 mg of ipilimumab per kilogram every 3 weeks for 4 doses (n=315)

3 arms: nivolumab alone, nivolumab combined with ipilimumab, ipilumab alone

double-blind

Parallel groups

Sample size: 314/315

Primary endpoint: PFS, OS

FU duration:

nivolumab (1 mg per kilogram)and ipilimumab (3 mg per kilogram of body weight) combined once every 3 weeks for four doses followed by nivolumab (3 mg per kilogram) every 2 weeks until the occurrence of disease progression or unacceptable toxic effects (n=-9)

vs.

(n=-9)

double-blind

Parallel groups

Sample size: -9/-9

Primary endpoint: investigator-assessed, confirmed objective response

FU duration:

phase 2. The primary end point was the rate of investigator-assessed, confirmed objective response among patients with BRAF V600 wild-type tumors

3 mg of nivolumab per kilogram of body weight every 2 weeks (n=316)

vs.

3 mg of ipilimumab per kilogram every 3 weeks for 4 doses (n=315)

3 arms: nivolumab alone, nivolumab combined with ipilimumab, ipilumab alone

double-blind

Parallel groups

Sample size: 316/315

Primary endpoint: PFS, OS

FU duration:

OS 1.09 [0.68; 1.75]

PFS 0.84 [0.57; 1.23]

Adverse events leading to discontinuation of drug 0.63 [0.23; 1.69]

overall response rate 0.99 [0.58; 1.67]

Grade 3 or 4 drug-related adverse events 1.75 [0.73; 4.18]

serious drug-related adverse events 6.61 [0.83; 52.57]

intravenous pembrolizumab at 2 mg/kg every 3 weeks (n=89)

vs.

intravenous pembrolizumab at 10 mg/kg every 3 weeks (n=84)

open-label

Parallel groups

Sample size: 89/84

Primary endpoint: ORR

FU duration:

PFS 0.57 [0.45; 0.73] median 2.9 mo vs. 2.7 mo

Vitiligo any grade 4.80 [1.07; 21.61]

Vitiligo grade 3-4 NaN [NaN; NaN]

PFS 0.50 [0.39; 0.64] median 2.9 mo vs. 2.7 mo

Vitiligo any grade 4.30 [0.94; 19.61]

Vitiligo grade 3-4 NaN [NaN; NaN]

Pembrolizumab 2 mg/kg IV Q3W (n=180)

vs.

investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide) (n=179)

3 arms ntravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy

open design

Parallel groups

Sample size: 180/179

Primary endpoint: PFS

FU duration:

phase 2

intravenous pembrolizumab 10 mg/kg every 3 weeks (n=181)

vs.

investigator-choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine, or oral temozolomide) (n=179)

3 arms ntravenous pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy

open design

Parallel groups

Sample size: 181/179

Primary endpoint: PFS

FU duration:

phase 2

OS 0.68 [0.53; 0.87] median NA vs. 16 months

PFS 0.58 [0.46; 0.73]

Grade 3 or 4 drug-related adverse events 0.67 [0.45; 0.98]

Vitiligo any grade 5.76 [2.03; 16.31]

Vitiligo grade 3-4 NaN [NaN; NaN]

OS 0.68 [0.53; 0.87] median NA vs. 16 months

PFS 0.58 [0.47; 0.72]

Grade 3 or 4 drug-related adverse events 0.51 [0.33; 0.78]

Vitiligo any grade 7.16 [2.56; 20.01]

Vitiligo grade 3-4 NaN [NaN; NaN]

pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks (n=-9)

vs.

four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks (n=-9)

3 arms: pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks

12% of second line patients was included

open-label

Parallel groups

Sample size: -9/-9

Primary endpoint: PFS, OS

FU duration:

Pembrolizumab Every 3 Weeks (n=277)

vs.

Ipilimumab (Participants receive ipilimumab, 3 mg/kg IV, once every 3 weeks for a total oPembrolizumab Every 2 Weeks (Participants receive pembrolizumab, 10 mg intravenously (IV), once every 2 weeks for up to 2 years) 2/ Pembrolizumab Every 3 Weeks (P (n=278)

3 arms: pembrolizumab (at a dose of 10 mg per kilogram of body weight) every 2 weeks or every 3 weeks or four doses of ipilimumab (at 3 mg per kilogram) every 3 weeks.

12% of second line patients was included

open label

Parallel groups

Sample size: 277/278

Primary endpoint: PFS, OS

FU duration:

recurrence free survival 0.57 [0.43; 0.75] Demonstrated

PFS LP-D1 positif 0.54 [0.42; 0.69]

PFS PD-L1 negatif 0.47 [0.26; 0.85]

PFS 0.57 [0.43; 0.75]

Grade 3 or 4 drug-related adverse events 4.35 [2.61; 7.26]

Vitiligo any grade 2.96 [1.34; 6.52]

Vitiligo grade 3-4 NaN [NaN; NaN]

Pembrolizumab (Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 1 year) (n=514)

vs.

placebo (n=505)

double-blind

Parallel groups

Sample size: 514/505

Primary endpoint: Recurrence-free survival ,

FU duration: 15 months (median)

OS 0.96 [0.76; 1.21]

PFS 1.04 [0.84; 1.29]

OS 0.84 [0.66; 1.07]

PFS 0.84 [0.67; 1.06]

DMFS 0.84 [0.66; 1.07]

PFS 0.87 [0.76; 1.00]

OS 0.96 [0.83; 1.12]

DMFS 0.93 [0.81; 1.07]

PFS 0.77 [0.62; 0.95]

OS 0.91 [0.72; 1.15]

OS 1.61 [1.01; 2.56]

rIFN-alpha2b (n=-9)

vs.

observation (n=-9)

4 arms: IFN-alpha2b versus rIFN-gamma versus ISCADOR M versus observation

Sample size: -9/-9

Primary endpoint:

FU duration: 8.2 years (median)

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 4.65 years

pegylated interferon alfa-2b 6 mug/kg per week for 8 weeks (induction) then 3 mug/kg per week (maintenance) for an intended duration of 5 years (n=627)

vs.

(n=629)

Sample size: 627/629

Primary endpoint: recurrence-free survival

FU duration: 3.8 years

intermediate-dose interferon alfa-2b duration 1 (n=-9)

vs.

duration 2 (n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: 72·4 months

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration:

(n=-9)

vs.

(n=-9)

Sample size: -9/-9

Primary endpoint:

FU duration: