All patients
Age < 65y (younger) Age > 65y Age > 75y (older) ECOG 0 ECOG 1 Gender, female Gender, male LDH > ULN LDH ≤ULN metastasis (brain) NO metastasis (brain) YES metastasis (liver ) PD-L1 < 5% 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) Prior anti-CTLA4 benefit NO Prior anti-CTLA4 benefit YES stage III (locally advanced) stage IV (metastatic) stage M0/M1A/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 - L1 - BRAF wild, anti-PD-(L)1 vs. all, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results CheckMate 066, 2015 0.42 [0.25; 0.72]
CheckMate 066 DUPLICATE, 2015 0.36 [0.24; 0.55]
IMspire-170, 2020 1.06 [0.69; 1.62]
0.55 [0.27 ; 1.10 ] CheckMate 066, 2015, CheckMate 066 DUPLICATE, 2015, IMspire-170, 2020 3 86% 1,282 low not evaluable deaths (OS) (extension)detailed results CheckMate 066, 2015 0.46 [0.36; 0.59]
0.46 [0.36 ; 0.59 ] CheckMate 066, 2015 1 0% 418 NA not evaluable PFS (extension)detailed results CheckMate 066, 2015 0.42 [0.33; 0.53]
0.42 [0.33 ; 0.53 ] CheckMate 066, 2015 1 0% 418 NA not evaluable progression or deaths (PFS)detailed results CheckMate 066, 2015 0.43 [0.34; 0.55]
CheckMate 066 DUPLICATE, 2015 0.43 [0.34; 0.55]
IMspire-170, 2020 1.15 [0.88; 1.50]
0.60 [0.32 ; 1.12 ] CheckMate 066, 2015, CheckMate 066 DUPLICATE, 2015, IMspire-170, 2020 3 95% 1,282 low not evaluable DCRdetailed results IMspire-170, 2020 0.91 [0.63; 1.32]
0.91 [0.63 ; 1.32 ] IMspire-170, 2020 1 0% 446 NA not evaluable DOR (extension)detailed results CheckMate 066, 2015 3.45 [1.46; 8.18]
3.45 [1.46 ; 8.18 ] CheckMate 066, 2015 1 0% 120 NA not evaluable objective responses (ORR)detailed results CheckMate 066, 2015 4.06 [2.52; 6.54]
CheckMate 066 DUPLICATE, 2015 4.06 [2.52; 6.54]
IMspire-170, 2020 0.77 [0.50; 1.17]
2.32 [0.75 ; 7.18 ] CheckMate 066, 2015, CheckMate 066 DUPLICATE, 2015, IMspire-170, 2020 3 95% 1,282 low not evaluable objective responses (ORR) (extension)detailed results CheckMate 066, 2015 4.50 [2.79; 7.25]
4.50 [2.79 ; 7.25 ] CheckMate 066, 2015 1 0% 418 NA not evaluable AE (any grade)detailed results CheckMate 066, 2015 0.78 [0.34; 1.76]
IMspire-170, 2020 14.27 [3.34; 61.03]
3.12 [0.18 ; 53.89 ] CheckMate 066, 2015, IMspire-170, 2020 2 91% 847 low not evaluable AE (grade 3-4)detailed results CheckMate 066, 2015 0.84 [0.56; 1.25]
IMspire-170, 2020 4.03 [2.70; 6.00]
1.84 [0.39 ; 8.56 ] CheckMate 066, 2015, IMspire-170, 2020 2 97% 847 moderate not evaluable AE leading to death (grade 5)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
IMspire-170, 2020 1.39 [0.43; 4.44]
1.35 [0.44 ; 4.12 ] CheckMate 066, 2015, IMspire-170, 2020 2 0% 847 moderate not evaluable AE leading to treatment discontinuation (any grade)detailed results CheckMate 066, 2015 0.55 [0.28; 1.10]
0.55 [0.28 ; 1.10 ] CheckMate 066, 2015 1 0% 411 NA not evaluable AE leading to treatment discontinuation (grade 3-4)detailed results CheckMate 066, 2015 0.61 [0.29; 1.28]
0.61 [0.29 ; 1.28 ] CheckMate 066, 2015 1 0% 411 NA not evaluable SAE (any grade)detailed results CheckMate 066, 2015 0.73 [0.49; 1.10]
0.73 [0.49 ; 1.10 ] CheckMate 066, 2015 1 0% 411 NA not evaluable SAE (grade 3-4)detailed results CheckMate 066, 2015 0.74 [0.47; 1.17]
0.74 [0.47 ; 1.17 ] CheckMate 066, 2015 1 0% 411 NA not evaluable STRAE (any grade)detailed results CheckMate 066, 2015 1.06 [0.54; 2.07]
1.06 [0.54 ; 2.07 ] CheckMate 066, 2015 1 0% 411 NA not evaluable STRAE (grade 3-4)detailed results CheckMate 066, 2015 0.99 [0.44; 2.27]
0.99 [0.44 ; 2.27 ] CheckMate 066, 2015 1 0% 411 NA not evaluable TRAE (any grade)detailed results CheckMate 066, 2015 0.93 [0.60; 1.46]
0.93 [0.60 ; 1.46 ] CheckMate 066, 2015 1 0% 411 NA not evaluable TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.62 [0.35; 1.08]
0.62 [0.35 ; 1.08 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Abdominal pain TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Alopecia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Anaemia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Arthralgia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Asthenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.50 [0.02; 14.88]
0.50 [0.02 ; 14.88 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Constipation TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Cough TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Decreased appetite TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Diarrhoea TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.18; 22.23]
2.00 [0.18 ; 22.23 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Dry skin TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Fatigue TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.25 [0.01; 5.51]
0.25 [0.01 ; 5.51 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Headache TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Hypersensitivity TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
2.00 [0.07 ; 59.80 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Hypothyroidism TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Increase AST TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.06; 16.02]
1.00 [0.06 ; 16.02 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Increased ALT TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.18; 22.23]
2.00 [0.18 ; 22.23 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Infusion-related reactions TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Leucopenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.12 [0.01; 2.33]
0.12 [0.01 ; 2.33 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Maculopapular rash TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
2.00 [0.07 ; 59.80 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Myalgia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Nausea TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Neutropenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.05 [0.00; 0.92]
0.05 [0.00 ; 0.92 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Pancytopenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.16 [0.01; 3.29]
0.16 [0.01 ; 3.29 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Paraesthesia TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Pruritus TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
2.00 [0.07 ; 59.80 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Pyrexia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.50 [0.02; 14.88]
0.50 [0.02 ; 14.88 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Rash TRAE (grade 3-4)detailed results CheckMate 066, 2015 2.00 [0.07; 59.80]
2.00 [0.07 ; 59.80 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Thrombocytopenia TRAE (grade 3-4)detailed results CheckMate 066, 2015 0.05 [0.00; 0.82]
0.05 [0.00 ; 0.82 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Vitiligo TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.02; 50.40]
1.00 [0.02 ; 50.40 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Vomiting TRAE (grade 3-4)detailed results CheckMate 066, 2015 1.00 [0.06; 16.02]
1.00 [0.06 ; 16.02 ] CheckMate 066, 2015 1 0% 411 NA not evaluable Abdominal pain AE (grade 3-4)detailed results IMspire-170, 2020 0.98 [0.14; 7.03]
0.98 [0.14 ; 7.03 ] IMspire-170, 2020 1 0% 436 NA not evaluable Anaemia AE (grade 3-4)detailed results IMspire-170, 2020 1.74 [0.50; 6.04]
1.74 [0.50 ; 6.04 ] IMspire-170, 2020 1 0% 436 NA not evaluable Arthralgia AE (grade 3-4)detailed results IMspire-170, 2020 0.98 [0.02; 49.71]
0.98 [0.02 ; 49.71 ] IMspire-170, 2020 1 0% 436 NA not evaluable Asthenia AE (grade 3-4)detailed results IMspire-170, 2020 1.74 [0.50; 6.04]
1.74 [0.50 ; 6.04 ] IMspire-170, 2020 1 0% 436 NA not evaluable Constipation AE (grade 3-4)detailed results IMspire-170, 2020 0.98 [0.02; 49.71]
0.98 [0.02 ; 49.71 ] IMspire-170, 2020 1 0% 436 NA not evaluable Decreased appetite AE (grade 3-4)detailed results IMspire-170, 2020 1.97 [0.07; 58.97]
1.97 [0.07 ; 58.97 ] IMspire-170, 2020 1 0% 436 NA not evaluable Dermatitis acneiform AE (grade 3-4)detailed results Out of scale IMspire-170, 2020 22.68 [1.32; 388.47]
22.68 [1.32 ; 388.47 ] IMspire-170, 2020 1 0% 436 NA not evaluable Diarrhoea AE (grade 3-4)detailed results IMspire-170, 2020 4.44 [1.47; 13.42]
4.44 [1.47 ; 13.42 ] IMspire-170, 2020 1 0% 436 NA not evaluable Fatigue AE (grade 3-4)detailed results IMspire-170, 2020 1.65 [0.39; 7.00]
1.65 [0.39 ; 7.00 ] IMspire-170, 2020 1 0% 436 NA not evaluable Headache AE (grade 3-4)detailed results IMspire-170, 2020 1.97 [0.07; 58.97]
1.97 [0.07 ; 58.97 ] IMspire-170, 2020 1 0% 436 NA not evaluable Hypertension AE (grade 3-4)detailed results IMspire-170, 2020 1.77 [0.73; 4.30]
1.77 [0.73 ; 4.30 ] IMspire-170, 2020 1 0% 436 NA not evaluable Increase AST AE (grade 3-4)detailed results IMspire-170, 2020 3.00 [0.60; 15.03]
3.00 [0.60 ; 15.03 ] IMspire-170, 2020 1 0% 436 NA not evaluable Increased ALT AE (grade 3-4)detailed results IMspire-170, 2020 1.99 [0.49; 8.06]
1.99 [0.49 ; 8.06 ] IMspire-170, 2020 1 0% 436 NA not evaluable Increased Lipase Level AE (grade 3-4)detailed results IMspire-170, 2020 2.00 [0.59; 6.74]
2.00 [0.59 ; 6.74 ] IMspire-170, 2020 1 0% 436 NA not evaluable Nausea AE (grade 3-4)detailed results IMspire-170, 2020 10.02 [0.54; 184.60]
10.02 [0.54 ; 184.60 ] IMspire-170, 2020 1 0% 436 NA not evaluable Peripheral oedema AE (grade 3-4)detailed results IMspire-170, 2020 0.98 [0.06; 15.80]
0.98 [0.06 ; 15.80 ] IMspire-170, 2020 1 0% 436 NA not evaluable Pruritus AE (grade 3-4)detailed results IMspire-170, 2020 0.98 [0.02; 49.71]
0.98 [0.02 ; 49.71 ] IMspire-170, 2020 1 0% 436 NA not evaluable Pyrexia AE (grade 3-4)detailed results IMspire-170, 2020 6.03 [0.72; 50.50]
6.03 [0.72 ; 50.50 ] IMspire-170, 2020 1 0% 436 NA not evaluable Rash AE (grade 3-4)detailed results IMspire-170, 2020 7.83 [1.77; 34.66]
7.83 [1.77 ; 34.66 ] IMspire-170, 2020 1 0% 436 NA not evaluable Rash maculopapular AE (grade 3-4)detailed results IMspire-170, 2020 7.98 [0.42; 151.89]
7.98 [0.42 ; 151.89 ] IMspire-170, 2020 1 0% 436 NA not evaluable Sepsis AE (grade 3-4)detailed results IMspire-170, 2020 12.08 [0.67; 217.70]
12.08 [0.67 ; 217.70 ] IMspire-170, 2020 1 0% 436 NA not evaluable Vomiting AE (grade 3-4)detailed results IMspire-170, 2020 2.49 [0.48; 12.97]
2.49 [0.48 ; 12.97 ] IMspire-170, 2020 1 0% 436 NA not evaluable 0.0 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-09-30 18:52 +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: 128
- treatments: 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