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 IIIa stage IIIb stage IIIc stage IV (metastatic) stage M0 stage M0/M1A/M1B stage M1A stage M1B stage M1C stage M1C (with brain metastasis)
Top evidence (RCT only, high risk of bias excluded)
Best available evidence (possibly low or very low)
All RCTs
All studies (RCT+OBS)
metastatic/adv melanoma (mML), anti-PD-(L)1 vs. Standard of Care (SoC), meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results IMspire-150 (BRAF mutant), 2020 0.85 [0.65; 1.12]
KEYNOTE-002 (10 mg/kg), 2015 0.74 [0.57; 0.96]
KEYNOTE-002 (2 mg/kg), 2015 0.86 [0.67; 1.10]
KEYNOTE-022, 2019 0.76 [0.41; 1.40]
0.81 [0.70 ; 0.94 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 0% 1,353 moderate not evaluable progression or deaths (PFS)detailed results IMspire-150 (BRAF mutant), 2020 0.78 [0.63; 0.97]
KEYNOTE-002 (10 mg/kg), 2015 0.50 [0.39; 0.64]
KEYNOTE-002 (2 mg/kg), 2015 0.57 [0.45; 0.73]
KEYNOTE-022, 2019 0.66 [0.40; 1.08]
0.62 [0.49 ; 0.77 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 61% 1,353 moderate not evaluable DORdetailed results KEYNOTE-022, 2019 0.41 [0.20; 0.83]
0.41 [0.20 ; 0.83 ] KEYNOTE-022, 2019 1 0% 81 NA not evaluable objective responses (ORR)detailed results IMspire-150 (BRAF mutant), 2020 1.19 [0.83; 1.71]
KEYNOTE-002 (10 mg/kg), 2015 8.16 [3.74; 17.80]
KEYNOTE-002 (2 mg/kg), 2015 6.11 [2.77; 13.47]
KEYNOTE-022, 2019 0.68 [0.32; 1.47]
2.47 [0.82 ; 7.40 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 91% 1,353 low not evaluable AE (any grade)detailed results KEYNOTE-022, 2019 2.03 [0.18; 23.06]
2.03 [0.18 ; 23.06 ] KEYNOTE-022, 2019 1 0% 120 NA not evaluable AE (grade 3-4)detailed results KEYNOTE-022, 2019 2.44 [1.17; 5.12]
2.44 [1.17 ; 5.12 ] KEYNOTE-022, 2019 1 0% 120 NA not evaluable AE leading to death (grade 5)detailed results IMspire-150 (BRAF mutant), 2020 1.23 [0.42; 3.56]
KEYNOTE-022, 2019 4.10 [0.18; 92.93]
1.39 [0.51 ; 3.81 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-022, 2019 2 0% 631 low not evaluable AE leading to treatment discontinuation (any grade)detailed results IMspire-150 (BRAF mutant), 2020 0.78 [0.47; 1.29]
KEYNOTE-022, 2019 2.58 [1.16; 5.75]
1.36 [0.42 ; 4.40 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-022, 2019 2 84% 631 low not evaluable STRAE (any grade)detailed results IMspire-150 (BRAF mutant), 2020 1.24 [0.85; 1.81]
1.24 [0.85 ; 1.81 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable TRAE (any grade)detailed results IMspire-150 (BRAF mutant), 2020 0.82 [0.11; 5.85]
KEYNOTE-002 (10 mg/kg), 2015 0.76 [0.45; 1.26]
KEYNOTE-002 (2 mg/kg), 2015 0.56 [0.34; 0.93]
KEYNOTE-022, 2019 1.36 [0.29; 6.34]
0.68 [0.48 ; 0.96 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 0% 1,330 moderate not evaluable TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 1.41 [0.93; 2.12]
KEYNOTE-002 (10 mg/kg), 2015 0.54 [0.32; 0.91]
KEYNOTE-002 (2 mg/kg), 2015 0.44 [0.25; 0.76]
KEYNOTE-022, 2019 3.60 [1.67; 7.74]
1.02 [0.45 ; 2.30 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 4 89% 1,330 moderate not evaluable TRAE leading to death (grade 5)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
KEYNOTE-022, 2019 2.02 [0.07; 61.28]
1.62 [0.21 ; 12.60 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 3 0% 819 moderate not evaluable TRAE leading to discontinuation (any grade)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.65 [0.70; 3.87]
KEYNOTE-002 (2 mg/kg), 2015 0.85 [0.32; 2.25]
KEYNOTE-022, 2019 2.67 [1.18; 6.03]
1.62 [0.86 ; 3.05 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015, KEYNOTE-022, 2019 3 36% 819 moderate not evaluable TRAE leading to discontinuation (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 2.73 [0.85; 8.76]
KEYNOTE-002 (2 mg/kg), 2015 1.46 [0.40; 5.25]
2.06 [0.87 ; 4.87 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Alopecia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Anaemia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.05 [0.00; 0.88]
KEYNOTE-002 (2 mg/kg), 2015 0.10 [0.01; 0.81]
0.08 [0.01 ; 0.43 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Arthralgia TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 1.44 [0.48; 4.34]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.06; 15.39]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.06; 15.48]
1.30 [0.50 ; 3.42 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 low not evaluable Asthenia TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 2.47 [0.45; 13.60]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.06; 15.39]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.06; 15.48]
1.64 [0.45 ; 5.96 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 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 Colitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 2.90 [0.30; 28.13]
KEYNOTE-002 (2 mg/kg), 2015 0.48 [0.02; 14.37]
1.66 [0.25 ; 11.00 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Constipation TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Decreased appetite TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.30 [0.01; 6.77]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.58 [0.07 ; 4.55 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 moderate not evaluable Diarrhoea TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.53 [0.16; 1.76]
KEYNOTE-002 (10 mg/kg), 2015 1.28 [0.28; 5.81]
KEYNOTE-002 (2 mg/kg), 2015 0.16 [0.01; 3.17]
0.65 [0.27 ; 1.59 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 low not evaluable Dry skin TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 4.92 [0.22; 109.67]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
1.98 [0.25 ; 15.69 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 moderate 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 IMspire-150 (BRAF mutant), 2020 3.70 [0.38; 35.82]
KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.05; 1.10]
KEYNOTE-002 (2 mg/kg), 2015 0.23 [0.05; 1.11]
0.48 [0.10 ; 2.26 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 57% 1,210 moderate not evaluable Hepatitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 3.85 [0.17; 86.06]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
2.26 [0.20 ; 25.79 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 4.92 [0.22; 109.67]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
1.98 [0.25 ; 15.69 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 moderate not evaluable Hypophysitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.06; 57.80]
1.43 [0.11 ; 18.64 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Hypothyroidism TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate 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 Leucopenia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.07 [0.00; 1.17]
KEYNOTE-002 (2 mg/kg), 2015 0.07 [0.00; 1.17]
0.07 [0.01 ; 0.50 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Maculopapular rash TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 1.36 [0.78; 2.37]
KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.06; 57.80]
1.38 [0.80 ; 2.37 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 low not evaluable Myalgia TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 2.46 [0.22; 27.26]
KEYNOTE-002 (10 mg/kg), 2015 0.48 [0.02; 14.29]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.17; 21.50]
1.61 [0.35 ; 7.36 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 moderate not evaluable Nausea TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.17 [0.02; 1.40]
KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.03; 2.12]
KEYNOTE-002 (2 mg/kg), 2015 0.12 [0.01; 2.24]
0.18 [0.05 ; 0.69 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 moderate not evaluable Neutropenia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.08 [0.00; 1.39]
KEYNOTE-002 (2 mg/kg), 2015 0.08 [0.00; 1.40]
0.08 [0.01 ; 0.60 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Pancreatitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
1.42 [0.11 ; 18.63 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Paraesthesia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Peripheral neuropathy TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.24 [0.01; 5.29]
KEYNOTE-002 (2 mg/kg), 2015 0.24 [0.01; 5.32]
0.24 [0.03 ; 2.13 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate 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]
KEYNOTE-002 (10 mg/kg), 2015 5.81 [0.29; 116.90]
KEYNOTE-002 (2 mg/kg), 2015 1.93 [0.06; 57.80]
4.00 [0.65 ; 24.72 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 moderate not evaluable Pruritus TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 2.46 [0.22; 27.26]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
1.64 [0.27 ; 10.10 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 low not evaluable Pyrexia TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 1.22 [0.24; 6.13]
1.22 [0.24 ; 6.13 ] IMspire-150 (BRAF mutant), 2020 1 0% 511 NA not evaluable Rash TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.98 [0.53; 1.81]
KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.97 [0.53 ; 1.78 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 low not evaluable Thrombocytopenia TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.03; 2.12]
KEYNOTE-002 (2 mg/kg), 2015 0.12 [0.01; 2.24]
0.18 [0.03 ; 1.07 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Uveitis TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 1.92 [0.06; 57.48]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
1.42 [0.11 ; 18.63 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Vitiligo TRAE (grade 3-4)detailed results KEYNOTE-002 (10 mg/kg), 2015 0.96 [0.02; 48.41]
KEYNOTE-002 (2 mg/kg), 2015 0.96 [0.02; 48.69]
0.96 [0.06 ; 15.38 ] KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 2 0% 699 moderate not evaluable Vomiting TRAE (grade 3-4)detailed results IMspire-150 (BRAF mutant), 2020 0.48 [0.09; 2.52]
KEYNOTE-002 (10 mg/kg), 2015 0.23 [0.03; 2.12]
KEYNOTE-002 (2 mg/kg), 2015 0.24 [0.03; 2.13]
0.33 [0.11 ; 1.03 ] IMspire-150 (BRAF mutant), 2020, KEYNOTE-002 (10 mg/kg), 2015, KEYNOTE-002 (2 mg/kg), 2015 3 0% 1,210 moderate 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 2024-09-28 00:31 +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: 283,284,70,235,285,68,127,128,286,69,129
- treatments: 367,851,361,602,1070,671,865,744,696,1083,1281,1282,1283,1082,866,852,417,603,1051,876,853,1018,661,673,1049,1440,1561,854,374,953,672,1080,1560,1073,862,1562,1565,855,360,719,721,720,842,642,674,1085,863,503,847,982,359,575,577,576,869,1081,981,875,505,952,1021,1079,767,1071,1074,873,561,644,1251,1044,724,874,1043,1041,1042,940,1258,1563
