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)
studies
melanoma (ML), anti-CTLA-4 vs. chemotherapy, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results A3671009, 2013 0.88 [0.75; 1.04]
CA184-024, 2011 0.72 [0.59; 0.87]
0.80 [0.66 ; 0.98 ] A3671009, 2013, CA184-024, 2011 2 58% 1,157 moderate not evaluable deaths (OS) (extension)detailed results CA184-024, 2011 0.69 [0.57; 0.84]
0.69 [0.57 ; 0.84 ] CA184-024, 2011 1 0% NA not evaluable progression or deaths (PFS)detailed results CA184-024, 2011 0.76 [0.63; 0.92]
0.76 [0.63 ; 0.92 ] CA184-024, 2011 1 0% 502 NA not evaluable DCRdetailed results CA184-024, 2011 1.15 [0.79; 1.68]
1.15 [0.79 ; 1.68 ] CA184-024, 2011 1 0% 502 NA not evaluable objective responses (ORR)detailed results A3671009, 2013 1.14 [0.69; 1.88]
CA184-024, 2011 1.56 [0.91; 2.65]
1.32 [0.91 ; 1.90 ] A3671009, 2013, CA184-024, 2011 2 0% 1,157 moderate not evaluable AE (any grade)detailed results A3671009, 2013 2.22 [1.12; 4.38]
CA184-024, 2011 5.17 [1.48; 18.09]
2.86 [1.34 ; 6.10 ] A3671009, 2013, CA184-024, 2011 2 26% 1,142 moderate not evaluable AE (grade 3-4)detailed results A3671009, 2013 1.84 [1.35; 2.52]
CA184-024, 2011 3.39 [2.34; 4.94]
2.48 [1.36 ; 4.51 ] A3671009, 2013, CA184-024, 2011 2 83% 1,142 moderate not evaluable AE leading to death (grade 5)detailed results A3671009, 2013 1.71 [0.85; 3.45]
CA184-024, 2011 1.02 [0.02; 51.42]
1.68 [0.84 ; 3.36 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable AE leading to treatment discontinuation (any grade)detailed results A3671009, 2013 97.13 [5.95; 1585.40]
97.13 [5.95 ; 1585.40 ] A3671009, 2013 1 0% 644 NA not evaluable SAE (any grade)detailed results A3671009, 2013 3.19 [2.19; 4.65]
3.19 [2.19 ; 4.65 ] A3671009, 2013 1 0% 644 NA not evaluable TRAE (any grade)detailed results CA184-024, 2011 5.64 [3.80; 8.35]
5.64 [3.80 ; 8.35 ] CA184-024, 2011 1 0% 498 NA not evaluable TRAE (grade 3-4)detailed results CA184-024, 2011 11.25 [6.30; 20.10]
11.25 [6.30 ; 20.10 ] CA184-024, 2011 1 0% 498 NA not evaluable TRAE leading to death (grade 5)detailed results A3671009, 2013 7.00 [0.86; 57.23]
7.00 [0.86 ; 57.23 ] A3671009, 2013 1 0% 644 NA not evaluable Adrenal insufficiency TRAE (grade 3-4)detailed results A3671009, 2013 5.93 [0.30; 118.96]
5.93 [0.30 ; 118.96 ] A3671009, 2013 1 0% 644 NA not evaluable Colitis TRAE (grade 3-4)detailed results CA184-024, 2011 10.35 [0.56; 190.49]
10.35 [0.56 ; 190.49 ] CA184-024, 2011 1 0% 498 NA not evaluable Diarrhoea TRAE (grade 3-4)detailed results CA184-024, 2011 21.14 [1.23; 363.94]
21.14 [1.23 ; 363.94 ] CA184-024, 2011 1 0% 498 NA not evaluable Eye disorders TRAE (grade 3-4)detailed results A3671009, 2013 0.98 [0.02; 49.62]
0.98 [0.02 ; 49.62 ] A3671009, 2013 1 0% 644 NA not evaluable Hepatitis TRAE (grade 3-4)detailed results A3671009, 2013 3.94 [0.18; 87.81]
CA184-024, 2011 8.25 [0.43; 156.83]
5.81 [0.69 ; 49.23 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 low not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Hypothyroidism TRAE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Increase AST TRAE (grade 3-4)detailed results CA184-024, 2011 52.70 [7.19; 385.99]
52.70 [7.19 ; 385.99 ] CA184-024, 2011 1 0% 498 NA not evaluable Increased ALT TRAE (grade 3-4)detailed results CA184-024, 2011 32.40 [7.79; 134.72]
32.40 [7.79 ; 134.72 ] CA184-024, 2011 1 0% 498 NA not evaluable Pancreatitis TRAE (grade 3-4)detailed results A3671009, 2013 5.93 [0.30; 118.96]
5.93 [0.30 ; 118.96 ] A3671009, 2013 1 0% 644 NA not evaluable Pruritus TRAE (grade 3-4)detailed results CA184-024, 2011 10.35 [0.56; 190.49]
10.35 [0.56 ; 190.49 ] CA184-024, 2011 1 0% 498 NA not evaluable Rash TRAE (grade 3-4)detailed results CA184-024, 2011 6.16 [0.31; 123.62]
6.16 [0.31 ; 123.62 ] CA184-024, 2011 1 0% 498 NA not evaluable Thyroiditis TRAE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Abdominal pain AE (grade 3-4)detailed results A3671009, 2013 4.04 [1.13; 14.45]
CA184-024, 2011 0.43 [0.11; 1.68]
1.33 [0.15 ; 12.01 ] A3671009, 2013, CA184-024, 2011 2 82% 1,142 moderate not evaluable Asthenia AE (grade 3-4)detailed results A3671009, 2013 0.10 [0.01; 1.78]
CA184-024, 2011 0.17 [0.02; 1.39]
0.14 [0.02 ; 0.77 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 low not evaluable Chills AE (grade 3-4)detailed results CA184-024, 2011 1.02 [0.02; 51.42]
1.02 [0.02 ; 51.42 ] CA184-024, 2011 1 0% 498 NA not evaluable Constipation AE (grade 3-4)detailed results A3671009, 2013 0.98 [0.14; 7.01]
CA184-024, 2011 1.02 [0.02; 51.42]
0.99 [0.17 ; 5.73 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable Cough AE (grade 3-4)detailed results A3671009, 2013 1.97 [0.07; 58.81]
CA184-024, 2011 2.04 [0.07; 60.99]
2.00 [0.18 ; 22.13 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable Decreased appetite AE (grade 3-4)detailed results A3671009, 2013 14.32 [1.87; 109.52]
CA184-024, 2011 0.76 [0.17; 3.43]
3.03 [0.17 ; 53.71 ] A3671009, 2013, CA184-024, 2011 2 81% 1,142 low not evaluable Diarrhoea AE (grade 3-4)detailed results CA184-024, 2011 21.14 [1.23; 363.94]
21.14 [1.23 ; 363.94 ] CA184-024, 2011 1 0% 498 NA not evaluable Dyspnoea AE (grade 3-4)detailed results A3671009, 2013 4.00 [0.84; 18.98]
CA184-024, 2011 16.77 [0.96; 293.61]
5.55 [1.41 ; 21.79 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable Fatigue AE (grade 3-4)detailed results A3671009, 2013 3.90 [1.44; 10.57]
CA184-024, 2011 2.44 [1.21; 4.94]
2.86 [1.61 ; 5.08 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 low not evaluable Headache AE (grade 3-4)detailed results A3671009, 2013 1.97 [0.18; 21.82]
CA184-024, 2011 4.12 [0.46; 37.08]
2.94 [0.58 ; 14.91 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 low not evaluable Increase AST AE (grade 3-4)detailed results CA184-024, 2011 18.42 [5.64; 60.14]
18.42 [5.64 ; 60.14 ] CA184-024, 2011 1 0% 498 NA not evaluable Increased ALT AE (grade 3-4)detailed results CA184-024, 2011 34.83 [8.39; 144.67]
34.83 [8.39 ; 144.67 ] CA184-024, 2011 1 0% 498 NA not evaluable Nausea AE (grade 3-4)detailed results A3671009, 2013 1.39 [0.61; 3.18]
CA184-024, 2011 1.36 [0.30; 6.14]
1.38 [0.67 ; 2.86 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable Neutropenia AE (grade 3-4)detailed results A3671009, 2013 0.03 [0.00; 0.19]
0.03 [0.00 ; 0.19 ] A3671009, 2013 1 0% 644 NA not evaluable Peripheral oedema AE (grade 3-4)detailed results A3671009, 2013 4.97 [0.58; 42.77]
4.97 [0.58 ; 42.77 ] A3671009, 2013 1 0% 644 NA not evaluable Pruritus AE (grade 3-4)detailed results A3671009, 2013 5.93 [0.30; 118.96]
CA184-024, 2011 10.35 [0.56; 190.49]
7.90 [0.98 ; 63.82 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 low not evaluable Pyrexia AE (grade 3-4)detailed results A3671009, 2013 7.94 [0.42; 150.76]
CA184-024, 2011 1.02 [0.02; 51.42]
3.79 [0.36 ; 39.89 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable Rash AE (grade 3-4)detailed results A3671009, 2013 7.00 [0.86; 57.23]
CA184-024, 2011 6.16 [0.31; 123.62]
6.71 [1.20 ; 37.51 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable Thrombocytopenia AE (grade 3-4)detailed results A3671009, 2013 0.03 [0.00; 0.26]
0.03 [0.00 ; 0.26 ] A3671009, 2013 1 0% 644 NA not evaluable Vomiting AE (grade 3-4)detailed results A3671009, 2013 1.55 [0.66; 3.64]
CA184-024, 2011 2.07 [0.61; 6.95]
1.70 [0.85 ; 3.42 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable Weight decreased AE (grade 3-4)detailed results A3671009, 2013 0.98 [0.06; 15.76]
CA184-024, 2011 1.02 [0.06; 16.34]
1.00 [0.14 ; 7.12 ] A3671009, 2013, CA184-024, 2011 2 0% 1,142 moderate not evaluable 0.0 200.0 1.0 relative treatment effect www.metaEvidence.org 2024-09-30 16:07 +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: 2,283,284,70,235,285,68,127,128,286,69,129
- treatments: 504,850,329,558,579,549,868,502,741,556