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/M1A/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), ipilimumab alone vs. nivolumab based treatment, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.59 [1.22; 2.06]
CheckMate 238, 2017 0.87 [0.66; 1.14]
1.18 [0.65 ; 2.12 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 90% 1,537 low not evaluable deaths (OS) (extension)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.59 [1.31; 1.92]
1.59 [1.31 ; 1.92 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 631 NA not evaluable MFSdetailed results CheckMate 238, 2017 0.73 [0.56; 0.96]
0.73 [0.56 ; 0.96 ] CheckMate 238, 2017 1 0% 735 NA not evaluable PFS (extension)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.89 [1.56; 2.28]
1.89 [1.56 ; 2.28 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 631 NA not evaluable progression or deaths (PFS)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.75 [1.32; 2.33]
1.75 [1.32 ; 2.33 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 631 NA not evaluable RFS (extension)detailed results CheckMate 238, 2017 0.71 [0.59; 0.85]
0.71 [0.59 ; 0.85 ] CheckMate 238, 2017 1 0% 906 NA not evaluable RFS/DFSdetailed results CheckMate 238, 2017 0.65 [0.51; 0.83]
0.65 [0.51 ; 0.83 ] CheckMate 238, 2017 1 0% 906 NA not evaluable objective responses (ORR)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.29 [0.17; 0.49]
0.29 [0.17 ; 0.49 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 631 NA not evaluable objective responses (ORR) (extension)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.28 [0.20; 0.41]
0.28 [0.20 ; 0.41 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 631 NA not evaluable AE (any grade)detailed results CheckMate 238, 2017 0.49 [0.20; 1.23]
0.49 [0.20 ; 1.23 ] CheckMate 238, 2017 1 0% 905 NA not evaluable AE (grade 3-4)detailed results CheckMate 238, 2017 0.28 [0.21; 0.37]
0.28 [0.21 ; 0.37 ] CheckMate 238, 2017 1 0% 905 NA not evaluable AE leading to treatment discontinuation (any grade)detailed results CheckMate 238, 2017 0.15 [0.10; 0.21]
0.15 [0.10 ; 0.21 ] CheckMate 238, 2017 1 0% 905 NA not evaluable AE leading to treatment discontinuation (grade 3-4)detailed results CheckMate 238, 2017 0.11 [0.07; 0.18]
0.11 [0.07 ; 0.18 ] CheckMate 238, 2017 1 0% 905 NA not evaluable TRAE (any grade)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.99 [0.63; 1.56]
CheckMate 238, 2017 0.25 [0.15; 0.43]
0.50 [0.13 ; 1.93 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 93% 1,529 low not evaluable TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.40 [0.97; 2.03]
CheckMate 238, 2017 0.20 [0.14; 0.27]
0.53 [0.08 ; 3.59 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 98% 1,529 low not evaluable TRAE leading to death (grade 5)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88]
CheckMate 238, 2017 0.25 [0.01; 5.55]
0.43 [0.04 ; 4.86 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable TRAE leading to discontinuation (any grade)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.40 [0.88; 2.21]
CheckMate 238, 2017 0.12 [0.08; 0.17]
0.40 [0.04 ; 4.57 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 98% 1,529 low not evaluable TRAE leading to discontinuation (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.93 [1.14; 3.27]
CheckMate 238, 2017 0.09 [0.05; 0.15]
0.41 [0.02 ; 8.63 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 98% 1,529 low not evaluable Abdominal pain TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 4.05 [0.18; 90.07]
CheckMate 238, 2017 0.50 [0.02; 14.96]
1.56 [0.16 ; 15.46 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Adrenal insufficiency TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.05; 5.56]
CheckMate 238, 2017 0.50 [0.09; 2.74]
0.50 [0.12 ; 2.01 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Arthralgia TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03]
CheckMate 238, 2017 0.50 [0.05; 5.53]
0.50 [0.07 ; 3.56 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Asthenia TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.18; 22.39]
CheckMate 238, 2017 0.25 [0.03; 2.24]
0.67 [0.09 ; 5.18 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 37% 1,529 low not evaluable Colitis TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 8.64 [2.57; 29.01]
8.64 [2.57 ; 29.01 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Cough TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.25 [0.01; 5.58]
0.25 [0.01 ; 5.58 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Decreased appetite TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32]
2.02 [0.07 ; 60.32 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Diabetes TRAE (grade 3-4)detailed results CheckMate 238, 2017 2.01 [0.07; 59.97]
2.01 [0.07 ; 59.97 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Diarrhoea TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 2.08 [0.92; 4.69]
CheckMate 238, 2017 0.15 [0.07; 0.34]
0.56 [0.04 ; 7.32 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 95% 1,529 low not evaluable Dry skin TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88]
1.01 [0.02 ; 50.88 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Dyspnoea TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03]
0.50 [0.02 ; 15.03 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Fatigue TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.20; 5.03]
CheckMate 238, 2017 0.50 [0.09; 2.74]
0.72 [0.22 ; 2.33 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Gastrointestinal disorders TRAE (grade 3-4) detailed results CheckMate 238, 2017 0.10 [0.05; 0.20]
0.10 [0.05 ; 0.20 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Headache TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32]
CheckMate 238, 2017 0.14 [0.02; 1.15]
0.38 [0.03 ; 4.64 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 41% 1,529 low not evaluable Hepatitis TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88]
1.01 [0.02 ; 50.88 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Hepatobiliary disorders TRAE (grade 3-4) detailed results CheckMate 238, 2017 0.15 [0.07; 0.32]
0.15 [0.07 ; 0.32 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Hypersensitivity TRAE (grade 3-4)detailed results CheckMate 238, 2017 2.01 [0.07; 59.97]
2.01 [0.07 ; 59.97 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88]
CheckMate 238, 2017 1.00 [0.06; 16.07]
1.00 [0.10 ; 9.67 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Hypophysitis TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 5.10 [0.59; 43.89]
CheckMate 238, 2017 0.18 [0.04; 0.81]
0.87 [0.03 ; 23.14 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 84% 1,529 low not evaluable Hypothyroidism TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88]
CheckMate 238, 2017 0.50 [0.05; 5.53]
0.61 [0.08 ; 4.70 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Increase AST TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.67 [0.11; 4.03]
CheckMate 238, 2017 0.10 [0.02; 0.44]
0.24 [0.04 ; 1.52 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 61% 1,529 low not evaluable Increased ALT TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.26 [0.34; 4.75]
CheckMate 238, 2017 0.18 [0.07; 0.48]
0.46 [0.07 ; 3.00 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 81% 1,529 low not evaluable Increased lipase level TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.86 [0.39; 1.88]
0.86 [0.39 ; 1.88 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Maculopapular rash TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.05; 5.56]
CheckMate 238, 2017 0.05 [0.00; 0.95]
0.19 [0.02 ; 1.64 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 26% 1,529 low not evaluable Myalgia TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03]
0.50 [0.02 ; 15.03 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Nausea TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 4.05 [0.18; 90.07]
CheckMate 238, 2017 2.01 [0.07; 59.97]
2.94 [0.30 ; 29.07 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Pneumonitis TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.06; 16.16]
1.01 [0.06 ; 16.16 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Pruritic rash TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88]
1.01 [0.02 ; 50.88 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Pruritus TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.06; 16.16]
CheckMate 238, 2017 0.10 [0.01; 1.82]
0.33 [0.03 ; 3.19 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 22% 1,529 low not evaluable Pyrexia TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32]
CheckMate 238, 2017 0.25 [0.01; 5.55]
0.65 [0.07 ; 6.38 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 0% 1,529 low not evaluable Rash TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 5.10 [0.59; 43.89]
CheckMate 238, 2017 0.35 [0.13; 0.98]
1.12 [0.08 ; 15.14 ] CheckMate 067 (N vs I ; all population), 2015 (REV), CheckMate 238, 2017 2 79% 1,529 low not evaluable Renal and urinary disorders TRAE (grade 3-4) detailed results CheckMate 238, 2017 1.00 [0.02; 50.62]
1.00 [0.02 ; 50.62 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) detailed results CheckMate 238, 2017 0.12 [0.01; 2.36]
0.12 [0.01 ; 2.36 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Skin and subcutaneous tissue disorders TRAE (grade 3-4) detailed results CheckMate 238, 2017 0.18 [0.07; 0.46]
0.18 [0.07 ; 0.46 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Thyroiditis TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.02; 50.88]
1.01 [0.02 ; 50.88 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Vitiligo TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 0.50 [0.02; 15.03]
0.50 [0.02 ; 15.03 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Vomiting TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 1.01 [0.06; 16.16]
1.01 [0.06 ; 16.16 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable Weight decreased TRAE (grade 3-4)detailed results CheckMate 067 (N vs I ; all population), 2015 (REV) 2.02 [0.07; 60.32]
2.02 [0.07 ; 60.32 ] CheckMate 067 (N vs I ; all population), 2015 (REV) 1 0% 624 NA not evaluable 0.0 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-06-22 15:14 +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: 2,283,284,70,235,285,68,127,128,286,69,129
- treatments: 329,558
