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) previous systemic treatment (%) previous systemic treatment NO (%) 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), immune chekpoint inhibitors vs. Ipilimumab (10 mg/kg), meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 0.84 [0.71; 1.00]
CheckMate 238, 2017 0.87 [0.66; 1.14]
0.85 [0.73 ; 0.98 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 0% 1,633 low 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 progression or deaths (PFS)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 0.89 [0.66; 1.21]
0.89 [0.66 ; 1.21 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 727 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 DCRdetailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.19 [0.86; 1.63]
1.19 [0.86 ; 1.63 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 727 NA not evaluable objective responses (ORR)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.31 [0.86; 2.00]
1.31 [0.86 ; 2.00 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 727 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 Ascierto (ipi 10 vs 3 mg/kg), 2017 2.40 [1.76; 3.28]
CheckMate 238, 2017 0.25 [0.15; 0.43]
0.78 [0.09 ; 7.15 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 98% 1,631 low not evaluable TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 2.70 [1.86; 3.92]
CheckMate 238, 2017 0.20 [0.14; 0.27]
0.73 [0.06 ; 9.46 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 99% 1,631 low not evaluable TRAE leading to death (grade 5)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 2.00 [0.36; 10.99]
CheckMate 238, 2017 0.25 [0.01; 5.55]
1.08 [0.17 ; 6.95 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 25% 1,631 low not evaluable TRAE leading to discontinuation (any grade)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.97 [1.40; 2.78]
CheckMate 238, 2017 0.12 [0.08; 0.17]
0.48 [0.03 ; 7.65 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 99% 1,631 low not evaluable TRAE leading to discontinuation (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 2.27 [1.53; 3.38]
CheckMate 238, 2017 0.09 [0.05; 0.15]
0.44 [0.02 ; 11.01 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 99% 1,631 low not evaluable Abdominal pain TRAE (grade 3-4)detailed results CheckMate 238, 2017 0.50 [0.02; 14.96]
0.50 [0.02 ; 14.96 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Adrenal insufficiency TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
CheckMate 238, 2017 0.50 [0.09; 2.74]
0.66 [0.14 ; 3.02 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 0% 1,631 low not evaluable Arthralgia TRAE (grade 3-4)detailed results CheckMate 238, 2017 0.50 [0.05; 5.53]
0.50 [0.05 ; 5.53 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Asthenia TRAE (grade 3-4)detailed results CheckMate 238, 2017 0.25 [0.03; 2.24]
0.25 [0.03 ; 2.24 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Colitis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 2.16 [0.96; 4.84]
2.16 [0.96 ; 4.84 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 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 Ascierto (ipi 10 vs 3 mg/kg), 2017 1.84 [1.05; 3.21]
CheckMate 238, 2017 0.15 [0.07; 0.34]
0.53 [0.05 ; 6.23 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 96% 1,631 low not evaluable Endocrine disorders TRAE (grade 3-4) detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 2.30 [0.99; 5.36]
2.30 [0.99 ; 5.36 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Eye disorders TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 0.50 [0.02; 14.85]
0.50 [0.02 ; 14.85 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Fatigue TRAE (grade 3-4)detailed results CheckMate 238, 2017 0.50 [0.09; 2.74]
0.50 [0.09 ; 2.74 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Febrile neutropenia TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 3.99 [0.18; 88.89]
3.99 [0.18 ; 88.89 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Gastrointestinal disorders TRAE (grade 3-4) detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.82 [1.14; 2.91]
CheckMate 238, 2017 0.10 [0.05; 0.20]
0.43 [0.03 ; 7.39 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 98% 1,631 low not evaluable Guillain-Barré syndrome TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 3.99 [0.18; 88.89]
3.99 [0.18 ; 88.89 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Headache TRAE (grade 3-4)detailed results CheckMate 238, 2017 0.14 [0.02; 1.15]
0.14 [0.02 ; 1.15 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Hepatitis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 2.51 [0.48; 13.01]
2.51 [0.48 ; 13.01 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 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 Ascierto (ipi 10 vs 3 mg/kg), 2017 6.01 [0.30; 120.38]
CheckMate 238, 2017 2.01 [0.07; 59.97]
3.72 [0.39 ; 35.19 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 0% 1,631 low not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results CheckMate 238, 2017 1.00 [0.06; 16.07]
1.00 [0.06 ; 16.07 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Hypophysitis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.43 [0.54; 3.81]
CheckMate 238, 2017 0.18 [0.04; 0.81]
0.55 [0.07 ; 4.20 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 81% 1,631 low not evaluable Hypothyroidism TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
CheckMate 238, 2017 0.50 [0.05; 5.53]
0.79 [0.11 ; 5.64 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 0% 1,631 low not evaluable Increase AST TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 8.11 [1.01; 65.20]
CheckMate 238, 2017 0.10 [0.02; 0.44]
0.85 [0.01 ; 62.11 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 91% 1,631 low not evaluable Increased ALT TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 6.14 [1.36; 27.62]
CheckMate 238, 2017 0.18 [0.07; 0.48]
1.01 [0.03 ; 31.43 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 93% 1,631 low not evaluable Increased lipase level TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
1.99 [0.07 ; 59.56 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Infusion-related reactions TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 3.99 [0.18; 88.89]
3.99 [0.18 ; 88.89 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Maculopapular rash TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
CheckMate 238, 2017 0.05 [0.00; 0.95]
0.29 [0.01 ; 9.81 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 60% 1,631 low not evaluable Nausea 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 Nervous system disorders TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 8.03 [0.42; 152.51]
8.03 [0.42 ; 152.51 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Pancreatitis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
1.99 [0.07 ; 59.56 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Pancytopenia TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
1.99 [0.07 ; 59.56 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Pericarditis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
1.99 [0.07 ; 59.56 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Peripheral neuropathy TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 3.99 [0.18; 88.89]
3.99 [0.18 ; 88.89 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Pneumonitis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 8.03 [0.42; 152.51]
8.03 [0.42 ; 152.51 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Polymyalgia Rheumatica TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 0.50 [0.02; 14.85]
0.50 [0.02 ; 14.85 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Pruritic rash TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 0.50 [0.02; 14.85]
0.50 [0.02 ; 14.85 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Pruritus TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 0.99 [0.14; 7.10]
CheckMate 238, 2017 0.10 [0.01; 1.82]
0.41 [0.05 ; 3.68 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 40% 1,631 low not evaluable Pyrexia TRAE (grade 3-4)detailed results CheckMate 238, 2017 0.25 [0.01; 5.55]
0.25 [0.01 ; 5.55 ] CheckMate 238, 2017 1 0% 905 NA not evaluable Rash TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 2.51 [0.48; 13.01]
CheckMate 238, 2017 0.35 [0.13; 0.98]
0.84 [0.12 ; 5.71 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 75% 1,631 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 Ascierto (ipi 10 vs 3 mg/kg), 2017 8.03 [0.42; 152.51]
CheckMate 238, 2017 0.12 [0.01; 2.36]
1.00 [0.02 ; 59.41 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 74% 1,631 low not evaluable Skin and subcutaneous tissue disorders TRAE (grade 3-4) detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.40 [0.44; 4.45]
CheckMate 238, 2017 0.18 [0.07; 0.46]
0.48 [0.06 ; 3.68 ] Ascierto (ipi 10 vs 3 mg/kg), 2017, CheckMate 238, 2017 2 86% 1,631 low not evaluable Thyroiditis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 1.99 [0.07; 59.56]
1.99 [0.07 ; 59.56 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable Uveitis TRAE (grade 3-4)detailed results Ascierto (ipi 10 vs 3 mg/kg), 2017 0.50 [0.02; 14.85]
0.50 [0.02 ; 14.85 ] Ascierto (ipi 10 vs 3 mg/kg), 2017 1 0% 726 NA not evaluable 0.0 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-09-29 20:50 +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: 204,504,850,329,558,579,549,868,502,741,556,812,813,367,851,361,602,1070,671,865,744,696,1083,1281,1282,1283,1082,866,852,417,603,1051,876,853,1018,661,673,1049,1440,1561,854,374,953,672,1080,1560,1073,862,1562,1565,855,360,719,721,720,842,642,674,1085,863,503,847,982,359,575,577,576,869,1081,981,875,505,952,1021,1079,767,1071,1074,873,561,644,1251,1044,724,874,1043,1041,1042,940,1258,1563,746,745,856,634,861,416,864,769,980,369,743
