All patients
Age < 65y (younger) Age > 65y 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 PD-L1 < 1% PD-L1 < 5% PD-L1 > 1% PD-L1 > 5% stage III (locally advanced) 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)
studies
mML - 1st line (L1), nivolumab plus ipilimumab vs. ipilimumab based treatment, 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 2024-10-05 15:41 +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
studied treatment is better when TE > 1;
studied treatment is better when TE < 1;
pathologies: 285,68,127,128
- treatments: 416,864