All patients
Age < 65y (younger) Age > 65y Age > 75y (older) BRAF mutant BRAF wild type ECOG ⩾ 1 ECOG 0 ECOG 1 Gender, female Gender, male LDH > ULN LDH ≤ULN metastasis (brain) NO metastasis (brain) YES metastasis (liver ) PD-L1 < 1% PD-L1 < 5% PD-L1 > 1% PD-L1 > 5% PDL1 (TC0 and IC0 : <1% of TC and IC) PDL1 (TC1/2/3 or IC1/2/3 : ≥1% of TC or IC) Prior anti-CTLA4 benefit NO Prior anti-CTLA4 benefit YES stage III (locally advanced) stage IIIc stage IV (metastatic) stage M0 stage M0/M1A/M1B stage M1A stage M1B stage M1C
Top evidence (RCT only, high risk of bias excluded)
Best available evidence (possibly low or very low)
All RCTs
All studies (RCT+OBS)
mML - 1st line (L1), anti-PD-(L)1 vs. chemotherapy, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results CheckMate 066, 2015 0.42 [0.25; 0.72]
CheckMate 066 DUPLICATE, 2015 0.36 [0.24; 0.55]
IMspire-150 (BRAF mutant), 2020 0.85 [0.65; 1.12]
0.52 [0.29 ; 0.94 ] CheckMate 066, 2015, CheckMate 066 DUPLICATE, 2015, IMspire-150 (BRAF mutant), 2020 3 85% 1,350 low not evaluable deaths (OS) (extension)detailed results CheckMate 066, 2015 0.46 [0.36; 0.59]
0.46 [0.36 ; 0.59 ] CheckMate 066, 2015 1 0% 418 NA not evaluable PFS (extension)detailed results CheckMate 066, 2015 0.42 [0.33; 0.53]
0.42 [0.33 ; 0.53 ] CheckMate 066, 2015 1 0% 418 NA not evaluable progression or deaths (PFS)detailed results CheckMate 066, 2015 0.43 [0.34; 0.55]
CheckMate 066 DUPLICATE, 2015 0.43 [0.34; 0.55]
IMspire-150 (BRAF mutant), 2020 0.78 [0.63; 0.97]
0.53 [0.35 ; 0.79 ] CheckMate 066, 2015, CheckMate 066 DUPLICATE, 2015, IMspire-150 (BRAF mutant), 2020 3 89% 1,350 low not evaluable DOR (extension)detailed results CheckMate 066, 2015 3.45 [1.46; 8.18]
3.45 [1.46 ; 8.18 ] CheckMate 066, 2015 1 0% 120 NA not evaluable objective responses (ORR)detailed results CheckMate 066, 2015 4.06 [2.52; 6.54]
CheckMate 066 DUPLICATE, 2015 4.06 [2.52; 6.54]
IMspire-150 (BRAF mutant), 2020 1.19 [0.83; 1.71]
2.66 [1.12 ; 6.34 ] CheckMate 066, 2015, CheckMate 066 DUPLICATE, 2015, IMspire-150 (BRAF mutant), 2020 3 92% 1,350 low not evaluable objective responses (ORR) (extension)detailed results CheckMate 066, 2015 4.50 [2.79; 7.25]
4.50 [2.79 ; 7.25 ] CheckMate 066, 2015 1 0% 418 NA not evaluable AE (any grade)detailed results CheckMate 066, 2015 0.78 [0.34; 1.76]
0.78 [0.34 ; 1.76 ] CheckMate 066, 2015 1 0% 411 NA not evaluable AE (grade 3-4)detailed results CheckMate 066, 2015 0.84 [0.56; 1.25]
0.84 [0.56 ; 1.25 ] CheckMate 066, 2015 1 0% 411 NA not evaluable AE leading to death (grade 5)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
IMspire-150 (BRAF mutant), 2020 1.23 [0.42; 3.56]
1.21 [0.43 ; 3.38 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable AE leading to treatment discontinuation (any grade)detailed results CheckMate 066, 2015 0.55 [0.28; 1.10]
IMspire-150 (BRAF mutant), 2020 0.78 [0.47; 1.29]
0.69 [0.46 ; 1.04 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable AE leading to treatment discontinuation (grade 3-4)detailed results CheckMate 066, 2015 0.61 [0.29; 1.28]
0.61 [0.29 ; 1.28 ] CheckMate 066, 2015 1 0% 411 NA not evaluable SAE (any grade)detailed results CheckMate 066, 2015 0.73 [0.49; 1.10]
0.73 [0.49 ; 1.10 ] CheckMate 066, 2015 1 0% 411 NA not evaluable SAE (grade 3-4)detailed results CheckMate 066, 2015 0.74 [0.47; 1.17]
0.74 [0.47 ; 1.17 ] CheckMate 066, 2015 1 0% 411 NA not evaluable STRAE (any grade)detailed results CheckMate 066, 2015 1.06 [0.54; 2.07]
IMspire-150 (BRAF mutant), 2020 1.24 [0.85; 1.81]
1.20 [0.86 ; 1.66 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable STRAE (grade 3-4)detailed results CheckMate 066, 2015 0.99 [0.44; 2.27]
0.99 [0.44 ; 2.27 ] CheckMate 066, 2015 1 0% 411 NA not evaluable TRAE (any grade)detailed results CheckMate 066, 2015 0.93 [0.60; 1.46]
IMspire-150 (BRAF mutant), 2020 0.82 [0.11; 5.85]
0.93 [0.60 ; 1.43 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.62 [0.35; 1.08]
IMspire-150 (BRAF mutant), 2020 1.41 [0.93; 2.12]
0.95 [0.43 ; 2.13 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 81% 922 low not evaluable Abdominal pain TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Alopecia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Anaemia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Arthralgia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
IMspire-150 (BRAF mutant), 2020 1.44 [0.48; 4.34]
1.40 [0.48 ; 4.06 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Asthenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.50 [0.02; 14.88]
IMspire-150 (BRAF mutant), 2020 2.47 [0.45; 13.60]
1.79 [0.39 ; 8.22 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Blood creatinine increased TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.61 [0.02; 18.27]
0.61 [0.02 ; 18.27 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable Chorioretinopathy TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.61 [0.02; 18.27]
0.61 [0.02 ; 18.27 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable Constipation TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Cough TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Decreased appetite TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
IMspire-150 (BRAF mutant), 2020 0.30 [0.01; 6.77]
0.48 [0.04 ; 5.47 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Diarrhoea TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.18; 22.23]
IMspire-150 (BRAF mutant), 2020 0.53 [0.16; 1.76]
0.69 [0.24 ; 2.02 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Dry skin TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
IMspire-150 (BRAF mutant), 2020 4.92 [0.22; 109.67]
2.66 [0.23 ; 30.36 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Erythema TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 7.41 [0.37; 148.78]
7.41 [0.37 ; 148.78 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable Fatigue TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.25 [0.01; 5.51]
IMspire-150 (BRAF mutant), 2020 3.70 [0.38; 35.82]
1.19 [0.09 ; 16.28 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 47% 922 low not evaluable Headache TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Hypersensitivity TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
IMspire-150 (BRAF mutant), 2020 4.92 [0.22; 109.67]
3.26 [0.33 ; 32.32 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Hypothyroidism TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Increase AST TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.06; 16.02]
1.00 [0.06 ; 16.02 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Increased ALT TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.18; 22.23]
2.00 [0.18 ; 22.23 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Increased lipase level TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.99 [0.64; 1.52]
0.99 [0.64 ; 1.52 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable Infusion-related reactions TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Leucopenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.12 [0.01; 2.33]
0.12 [0.01 ; 2.33 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Maculopapular rash TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
IMspire-150 (BRAF mutant), 2020 1.36 [0.78; 2.37]
1.37 [0.79 ; 2.37 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Myalgia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
IMspire-150 (BRAF mutant), 2020 2.46 [0.22; 27.26]
1.92 [0.25 ; 14.93 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Nausea TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
IMspire-150 (BRAF mutant), 2020 0.17 [0.02; 1.40]
0.25 [0.04 ; 1.62 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Neutropenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.05 [0.00; 0.92]
0.05 [0.00 ; 0.92 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Pancytopenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.16 [0.01; 3.29]
0.16 [0.01 ; 3.29 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Paraesthesia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Peripheral oedema TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 1.22 [0.02; 61.84]
1.22 [0.02 ; 61.84 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable Pneumonitis TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 4.92 [0.22; 109.67]
4.92 [0.22 ; 109.67 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable Pruritus TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
IMspire-150 (BRAF mutant), 2020 2.46 [0.22; 27.26]
2.29 [0.32 ; 16.34 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Pyrexia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.50 [0.02; 14.88]
IMspire-150 (BRAF mutant), 2020 1.22 [0.24; 6.13]
1.04 [0.24 ; 4.45 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Rash TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
IMspire-150 (BRAF mutant), 2020 0.98 [0.53; 1.81]
1.00 [0.54 ; 1.83 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Thrombocytopenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.05 [0.00; 0.82]
0.05 [0.00 ; 0.82 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Vitiligo TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Vomiting TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.06; 16.02]
IMspire-150 (BRAF mutant), 2020 0.48 [0.09; 2.52]
0.58 [0.14 ; 2.41 ] CheckMate 066, 2015, IMspire-150 (BRAF mutant), 2020 2 0% 922 low not evaluable Hypothyroidism AE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 1.22 [0.02; 61.84]
1.22 [0.02 ; 61.84 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable 0.0 10.0 1.0 relative treatment effect www.metaEvidence.org 2024-06-29 14:48 +02:00
TE: relative treatment effect (measured by a risk ratio, an odds ratio or an hazard ratio depending on what is reported in the papers);
k: number of studies; n: total number of patients;
ROB: risk of bias (ROB 2.0); Pub. bias: publication bias; OBS: observational studies; RCT: randomized clinical trials
pathologies: 285,68,127,128
- treatments: 367,851,361,602,1070,671,865,744,696,1083,1281,1282,1283,1082,866,852,417,603,1051,876,853,1018,661,673,1049,1440,854,374,1073,953,672,1080,862,855,360,719,721,720,842,642,674,1085,863,503,847,982,359,575,577,576,869,1081,981,875,505,952,1021,1079,767,1071,1074,873,561,644,1251,1044,724,874,1043,1041,1042,940,1258
