| Ipilimumab | melanoma, in adjuvant 1 - NOVARTIS | vs placebo | recurrence free survival by 24% fully demonstrated Grade 3–5 drug-related AEs by 107% adverse event distant metastasis free survival by 24% suggested death (overall survival) by 28% suggested progression or death (progression free survival PFS) by 24% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| recurrence free survival | 0.76 [0.64 0.90] | p=0.04 | 0 | 951 | 1 | EORTC 18071 (Eggermont), | | distant metastasis free survival | 0.76 [0.63 0.91] | p=0.04 | 0 | 951 | 1 | EORTC 18071 (Eggermont), | | death (overall survival) | 0.72 [0.58 0.89] | p=0.04 | 0 | 951 | 1 | EORTC 18071 (Eggermont), | | progression or death (progression free survival PFS) | 0.76 [0.64 0.90] | p=0.04 | 0 | 951 | 1 | EORTC 18071 (Eggermont), | | Grade 3–5 drug-related AEs | 2.07 [1.57 2.72] | p=0.04 | 0 | 945 | 1 | EORTC 18071 (Eggermont), |
| Trial | Studied treatment | Control | Patients |
|---|
| EORTC 18071 (Eggermont), 2015 | 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 | placebo | high risk patients who had undergone complete resection of stage III melanoma |
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| Nivolumab | melanoma, in adjuvant 1 - NOVARTIS | vs ipilimumab | recurrence free survival by 35% fully demonstrated Grade 3–5 drug-related AEs by 69% suggested progression or death (progression free survival PFS) by 35% suggested Adverse events leading to treatment discontinuation by 77% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| objective response (ORR) | no data | | Grade 3–5 drug-related AEs | 0.31 [0.23 0.43] | p=0.04 | 0 | 905 | 1 | CheckMate 238, | | recurrence free survival | 0.65 [0.51 0.83] | p=0.04 | 0 | 906 | 1 | CheckMate 238, | | distant metastasis free survival | no data | | death (overall survival) | no data | | progression or death (progression free survival PFS) | 0.65 [0.51 0.83] | p=0.04 | 0 | 906 | 1 | CheckMate 238, | | serious drug-related adverse events | no data | | toxic death | no data | | vitiligo any grade | no data | | vitiligo grade 3-4 | no data | | Adverse events leading to treatment discontinuation | 0.23 [0.16 0.33] | p=0.04 | 0 | 906 | 1 | CheckMate 238, |
| Trial | Studied treatment | Control | Patients |
|---|
| CheckMate 238, 2017 | nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks | ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks | patients with Complete Resection of Stage IIIb/c or Stage IV Melanoma |
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| Pembrolizumab | melanoma, in adjuvant 1 - NOVARTIS | vs placebo | recurrence free survival by 43% fully demonstrated vitiligo any grade by 196% adverse event Grade 3–5 drug-related AEs by 335% suggested progression or death (progression free survival PFS) by 43% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| objective response (ORR) | no data | | Grade 3–5 drug-related AEs | 4.35 [2.53 7.48] | p=0.04 | 0 | 1011 | 1 | KEYNOTE-054, | | recurrence free survival | 0.57 [0.43 0.75] | p=0.04 | 0 | 1019 | 1 | KEYNOTE-054, | | distant metastasis free survival | no data | | death (overall survival) | no data | | progression or death (progression free survival PFS) | 0.57 [0.43 0.75] | p=0.04 | 0 | 1019 | 1 | KEYNOTE-054, | | serious drug-related adverse events | no data | | toxic death | no data | | vitiligo any grade | 2.96 [1.32 6.65] | p=0.04 | 0 | 1011 | 1 | KEYNOTE-054, | | vitiligo grade 3-4 | 0.99 [0.02 49.80] | p=1.00 | 0 | 1011 | 1 | KEYNOTE-054, | | Adverse events leading to treatment discontinuation | no data |
| Trial | Studied treatment | Control | Patients |
|---|
| KEYNOTE-054, 2018 | Pembrolizumab (Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 1 year)
| placebo | patients with complete Resection of High-Risk Stage III Melanoma |
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| Vemurafenib | melanoma, in adjuvant 1 - NOVARTIS | vs placebo | progression or death (progression free survival PFS) by 35% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| objective response (ORR) | no data | | distant metastasis free survival | no data | | recurrence free survival | no data | | death (overall survival) | 0.72 [0.45 1.16] | p=1.00 | 0 | 498 | 1 | BRIM 8, | | progression or death (progression free survival PFS) | 0.65 [0.50 0.85] | p=0.04 | 0 | -18 | 1 | BRIM 8, |
| Trial | Studied treatment | Control | Patients |
|---|
| BRIM 8, 2018 | e twice-daily adjuvant oral vemurafenib 960 mg tablets for52 weeks (13×28-day cycles) | placebo | patients with resected,BRAFV600 mutation-positive melanoma: IC–IIIA–IIIB (cohort 1) or stage IIIC (cohort 2) |
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| Trametinib + dabrafenib | melanoma, in adjuvant 1 - NOVARTIS | vs placebo | aaa by 49% suggested death (overall survival) by 43% suggested progression or death (progression free survival PFS) by 53% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| objective response (ORR) | no data | | aaa | 0.51 [0.40 0.65] | p=0.04 | 0 | -18 | 1 | COMBI-AD, | | recurrence free survival | no data | | death (overall survival) | 0.57 [0.42 0.78] | p=0.04 | 0 | -18 | 1 | COMBI-AD, | | progression or death (progression free survival PFS) | 0.47 [0.39 0.57] | p=0.04 | 0 | -18 | 1 | COMBI-AD, |
| Trial | Studied treatment | Control | Patients |
|---|
| COMBI-AD, 2017 | dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months | placebo | Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma |
| |
| Trametinib + dabrafenib | | vs SOC | all NS | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| objective response (ORR) | no data | | aaa | no data | | recurrence free survival | no data | | death (overall survival) | no data | | progression or death (progression free survival PFS) | no data |
| Trial | Studied treatment | Control | Patients |
|---|
| COMBI neo, 2018 | | | |
| |
| Interferon alpha | melanoma, in adjuvant 1 - NOVARTIS | vs observation | progression or death (progression free survival PFS) by 13% suggested | | Endpoint | TE [95% CI] | p val | I2 | n | k | |
|---|
| distant metastasis free survival | 0.91 [0.80 1.02] | p=1.00 | 0 | -36 | 2 | EORTC18952 (Eggermont), EORTC18991 (Eggermont), | | death (overall survival) | 0.93 [0.84 1.03] | p=1.00 | 0 | -72 | 4 | EORTC18871/DKG 80-1 (Kleeberg), EORTC18952 (Eggermont), EORTC18991 (Eggermont), Nordic IFN Trial, | | progression or death (progression free survival PFS) | 0.87 [0.79 0.96] | p=0.04 | 0 | -72 | 4 | EORTC18871/DKG 80-1 (Kleeberg), EORTC18952 (Eggermont), EORTC18991 (Eggermont), Nordic IFN Trial, |
| Trial | Studied treatment | Control | Patients |
|---|
| EORTC18871/DKG 80-1 (Kleeberg), 2004 | rIFN-alpha2b | observation | High-risk stage II patients (thickness >3 mm) and stage III patients (positivelymph nodes) without distant metastasis | | EORTC18952 (Eggermont), 2005 | | | patients who had had a thick primary tumour (thickness4 mm) resected (stage IIb) or regional lymph node metastases dissected (stage III) | | EORTC18991 (Eggermont), 2008 | 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 | | patients with resected stage III melanoma | | Nordic IFN Trial, 2011 | intermediate-dose interferon alfa-2b duration 1 | duration 2 | patients with stage IIB-IIC or III resected cutaneous melanoma. |
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