| Vemurafenib | melanoma, in all type of patients | 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) |
| |
| Vemurafenib | melanoma, in adjuvant setting | 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) |
| |
| Encorafenib plus binimetinib | melanoma, in all type of patients | vs vemurafenib | progression or death (progression free survival PFS) by 46% suggested | | 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) | 0.54 [0.41 0.71] | p=0.04 | 0 | 383 | 1 | COLUMBUS, |
| Trial | Studied treatment | Control | Patients |
|---|
| COLUMBUS, 2018 | oral encorafenib 450 mg once daily plus oral binimetinib 45 mg twice daily | oral vemurafenib 960 mg twice daily | patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation |
| |
| Trametinib + dabrafenib | melanoma, in all type of patients | vs dabrafenib | death (overall survival) by 37% suggested progression or death (progression free survival PFS) by 37% suggested | | 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) | 0.63 [0.42 0.94] | p=0.04 | 0 | 423 | 1 | COMBI-D (Long), | | progression or death (progression free survival PFS) | 0.63 [0.50 0.80] | p=0.04 | 0 | 405 | 2 | Flaherty, COMBI-D (Long), |
| Trial | Studied treatment | Control | Patients |
|---|
| Flaherty, 2012 | dabrafenib (150 mg) plus trametinib (1 or 2 mg) | dabrafenib monotherapy | patients with metastatic melanoma and BRAF V600 mutations | | COMBI-D (Long), 2014 | dabrafenib and trametinib | dabrafenib monotherapy | previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation |
| |
| Trametinib + dabrafenib | | vs vemurafenib | death (overall survival) by 31% suggested progression or death (progression free survival PFS) by 44% suggested | | 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) | 0.69 [0.53 0.89] | p=0.04 | 0 | -18 | 1 | COMBI-V (Robert), | | progression or death (progression free survival PFS) | 0.56 [0.46 0.69] | p=0.04 | 0 | -18 | 1 | COMBI-V (Robert), |
| Trial | Studied treatment | Control | Patients |
|---|
| COMBI-V (Robert), 2015 | | | patients with metastatic melanoma with a BRAF V600 mutation |
| |
| Trametinib + dabrafenib | | 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 | | | |
| |
| Vemurafenib and cobimetinib | melanoma, in all type of patients | vs vemurafenib | progression or death (progression free survival PFS) by 49% suggested | | 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) | 0.51 [0.39 0.67] | p=0.04 | 0 | -18 | 1 | Larkin, |
| Trial | Studied treatment | Control | Patients |
|---|
| Larkin, 2014 | vemurafenib and cobimetinib | vemurafenib and placebo | patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma |
| |
