All patients
Age < 65y (younger) Age > 65y BRAF mutant BRAF wild type ECOG 0 ECOG 1 Gender, female Gender, male LDH > ULN LDH ≤ULN previous systemic treatment (%) previous systemic treatment NO (%) stage IIIa stage IIIb stage IIIc 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)
melanoma (ML), anti-CTLA-4 vs. ..., meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.55 [0.42; 0.72]
CheckMate 069 (all population), 2015 0.74 [0.43; 1.27]
CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 1.44 [0.46; 4.49]
0.67 [0.45 ; 0.98 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015, CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 3 38% 804 low not evaluable deaths (OS) (extension)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.52 [0.42; 0.64]
0.52 [0.42 ; 0.64 ] CheckMate 067 (NI vs I ; all population), 2015 1 0% 629 NA not evaluable PFS (extension)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.42 [0.35; 0.51]
CheckMate 069 (all population), 2015 0.36 [0.23; 0.57]
CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 0.47 [0.10; 2.27]
0.41 [0.35 ; 0.49 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015, CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 3 0% 804 low not evaluable progression or deaths (PFS)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.42 [0.31; 0.57]
CheckMate 069 (all population), 2015 0.38 [0.23; 0.63]
CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 0.38 [0.15; 0.98]
CheckMate 069 (BRAF wild type), 2015 0.40 [0.23; 0.69]
0.41 [0.32 ; 0.51 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015, CheckMate 069 (BRAF mutant) EXPLORATORY, 2015, CheckMate 069 (BRAF wild type), 2015 4 0% 913 low not evaluable objective responses (ORR)detailed results CheckMate 067 (NI vs I ; all population), 2015 6.11 [3.59; 10.39]
CheckMate 069 (all population), 2015 15.08 [8.07; 28.17]
CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 9.82 [0.45; 212.91]
CheckMate 069 (BRAF wild type), 2015 12.96 [3.47; 48.38]
9.81 [5.49 ; 17.55 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015, CheckMate 069 (BRAF mutant) EXPLORATORY, 2015, CheckMate 069 (BRAF wild type), 2015 4 39% 913 low not evaluable objective responses (ORR) (extension)detailed results CheckMate 067 (NI vs I ; all population), 2015 6.35 [4.38; 9.21]
CheckMate 069 (all population), 2015 12.20 [4.41; 33.76]
CheckMate 069 (BRAF mutant) EXPLORATORY, 2015 9.80 [0.45; 211.42]
CheckMate 069 (BRAF wild type), 2015 13.00 [3.48; 48.60]
7.18 [5.13 ; 10.04 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015, CheckMate 069 (BRAF mutant) EXPLORATORY, 2015, CheckMate 069 (BRAF wild type), 2015 4 0% 913 low not evaluable TRAE (any grade)detailed results CheckMate 067 (NI vs I ; all population), 2015 3.70 [1.95; 7.04]
CheckMate 069 (all population), 2015 0.75 [0.19; 2.97]
1.88 [0.40 ; 8.83 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 76% 764 low not evaluable TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 3.83 [2.74; 5.36]
CheckMate 069 (all population), 2015 3.77 [1.71; 8.31]
3.82 [2.81 ; 5.21 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable TRAE leading to death (grade 5)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.99 [0.02; 50.24]
0.99 [0.02 ; 50.24 ] CheckMate 067 (NI vs I ; all population), 2015 1 0% 624 NA not evaluable TRAE leading to discontinuation (any grade)detailed results CheckMate 067 (NI vs I ; all population), 2015 3.99 [2.72; 5.85]
CheckMate 069 (all population), 2015 4.18 [1.76; 9.91]
CheckMate 069 (BRAF wild type), 2015 3.39 [1.40; 8.19]
3.93 [2.84 ; 5.44 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015, CheckMate 069 (BRAF wild type), 2015 3 0% 872 low not evaluable TRAE leading to discontinuation (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 2.72 [1.82; 4.06]
CheckMate 069 (all population), 2015 4.14 [1.59; 10.74]
2.89 [2.00 ; 4.19 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Abdominal pain TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.50 [0.04; 5.49]
CheckMate 069 (all population), 2015 0.24 [0.01; 7.31]
0.39 [0.05 ; 2.78 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Adrenal insufficiency TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 6.06 [0.73; 50.62]
CheckMate 069 (all population), 2015 0.24 [0.02; 2.68]
1.27 [0.05 ; 30.32 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 74% 764 low not evaluable Arthralgia TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 3.99 [0.18; 88.92]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
1.78 [0.16 ; 20.38 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Asthenia TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.50 [0.04; 5.49]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
0.49 [0.06 ; 3.84 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Chills TRAE (grade 3-4)detailed results CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
0.49 [0.01 ; 24.92 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Colitis TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 1.08 [0.61; 1.93]
CheckMate 069 (all population), 2015 2.94 [0.81; 10.66]
1.50 [0.60 ; 3.76 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 48% 764 low not evaluable Constipation TRAE (grade 3-4)detailed results CheckMate 069 (all population), 2015 0.98 [0.03; 29.71]
0.98 [0.03 ; 29.71 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Cough TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.99 [0.02; 50.24]
0.99 [0.02 ; 50.24 ] CheckMate 067 (NI vs I ; all population), 2015 1 0% 624 NA not evaluable Decreased appetite TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 4.01 [0.45; 36.11]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
2.43 [0.36 ; 16.56 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Diarrhoea TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 1.66 [0.90; 3.06]
CheckMate 069 (all population), 2015 0.98 [0.31; 3.04]
1.48 [0.86 ; 2.53 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Dry skin TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.99 [0.02; 50.24]
0.99 [0.02 ; 50.24 ] CheckMate 067 (NI vs I ; all population), 2015 1 0% 624 NA not evaluable Dyspnoea TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 6.01 [0.30; 120.48]
CheckMate 069 (all population), 2015 3.00 [0.15; 61.17]
4.25 [0.51 ; 35.65 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Endocrine disorders TRAE (grade 3-4) detailed results CheckMate 069 (all population), 2015 1.24 [0.23; 6.63]
1.24 [0.23 ; 6.63 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Fatigue TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 4.45 [1.26; 15.77]
CheckMate 069 (all population), 2015 5.11 [0.27; 95.65]
4.55 [1.42 ; 14.53 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Gastrointestinal disorders TRAE (grade 3-4) detailed results CheckMate 069 (all population), 2015 2.22 [0.77; 6.34]
2.22 [0.77 ; 6.34 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Headache TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 1.99 [0.18; 22.10]
CheckMate 069 (all population), 2015 1.98 [0.09; 44.77]
1.99 [0.30 ; 13.36 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Hepatitis TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 10.08 [0.55; 185.32]
CheckMate 069 (all population), 2015 3.00 [0.15; 61.17]
5.62 [0.69 ; 45.61 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Hepatobiliary disorders TRAE (grade 3-4) detailed results CheckMate 069 (all population), 2015 15.93 [0.93; 273.74]
15.93 [0.93 ; 273.74 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 6.01 [0.30; 120.48]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
2.39 [0.22 ; 25.93 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Hypophysitis TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.99 [0.28; 3.47]
CheckMate 069 (all population), 2015 0.48 [0.07; 3.51]
0.81 [0.28 ; 2.33 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Hypothyroidism TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 1.99 [0.07; 59.55]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
1.09 [0.08 ; 14.28 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Increase AST TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 9.98 [2.31; 43.24]
CheckMate 069 (all population), 2015 7.32 [0.41; 131.94]
9.37 [2.54 ; 34.64 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Increased ALT TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 5.78 [2.20; 15.21]
CheckMate 069 (all population), 2015 10.83 [0.62; 189.76]
6.16 [2.46 ; 15.41 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Increased lipase level TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 3.04 [1.54; 5.98]
CheckMate 069 (all population), 2015 4.19 [0.51; 34.53]
3.13 [1.64 ; 5.97 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Maculopapular rash TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 6.06 [0.73; 50.62]
CheckMate 069 (all population), 2015 3.00 [0.15; 61.17]
4.80 [0.85 ; 27.23 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Myalgia TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 1.99 [0.07; 59.55]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
1.09 [0.08 ; 14.28 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Nausea TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 3.53 [0.73; 17.15]
CheckMate 069 (all population), 2015 0.48 [0.03; 7.91]
1.85 [0.30 ; 11.49 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 32% 764 low not evaluable Pneumonitis TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 3.00 [0.31; 29.00]
CheckMate 069 (all population), 2015 0.98 [0.09; 11.08]
1.78 [0.34 ; 9.33 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Pruritic rash TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.99 [0.02; 50.24]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
0.70 [0.04 ; 11.21 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Pruritus TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 6.06 [0.73; 50.62]
CheckMate 069 (all population), 2015 0.98 [0.03; 29.71]
3.64 [0.60 ; 22.10 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Pyrexia TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 1.99 [0.18; 22.10]
CheckMate 069 (all population), 2015 3.00 [0.15; 61.17]
2.34 [0.36 ; 15.32 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Rash TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 2.02 [0.68; 5.98]
CheckMate 069 (all population), 2015 5.11 [0.27; 95.65]
2.26 [0.82 ; 6.25 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Renal and urinary disorders TRAE (grade 3-4) detailed results CheckMate 069 (all population), 2015 0.98 [0.03; 29.71]
0.98 [0.03 ; 29.71 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) detailed results CheckMate 069 (all population), 2015 1.48 [0.15; 14.67]
1.48 [0.15 ; 14.67 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Skin and subcutaneous tissue disorders TRAE (grade 3-4) detailed results CheckMate 069 (all population), 2015 9.64 [0.55; 170.02]
9.64 [0.55 ; 170.02 ] CheckMate 069 (all population), 2015 1 0% 140 NA not evaluable Thyroiditis TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 1.99 [0.07; 59.55]
1.99 [0.07 ; 59.55 ] CheckMate 067 (NI vs I ; all population), 2015 1 0% 624 NA not evaluable Vitiligo TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.99 [0.02; 50.24]
CheckMate 069 (all population), 2015 0.49 [0.01; 24.92]
0.70 [0.04 ; 11.21 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Vomiting TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 7.09 [0.87; 57.98]
CheckMate 069 (all population), 2015 0.98 [0.03; 29.71]
4.11 [0.69 ; 24.63 ] CheckMate 067 (NI vs I ; all population), 2015, CheckMate 069 (all population), 2015 2 0% 764 low not evaluable Weight decreased TRAE (grade 3-4)detailed results CheckMate 067 (NI vs I ; all population), 2015 0.50 [0.02; 14.84]
0.50 [0.02 ; 14.84 ] CheckMate 067 (NI vs I ; all population), 2015 1 0% 624 NA not evaluable 0.2 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-11-05 19:10 +01:00
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: 2,283,284,70,235,285,68,127,128,286,69,129
- treatments: 504,850,329,558,579,549,868,502,741,556
