All patients
Age < 65y (younger) Age > 75y (older) cell type, non squamous cell cell type, squamous cell ECOG 0 ECOG 1 Gender, female Gender, male metastasis (bone) metastasis (brain) NO metastasis (brain) YES metastasis (liver ) PD-L1 < 1% PD-L1 > 1% PDL1 (TC0 and IC0 : <1% of TC and IC) PDL1 (TC1/2 or IC1/2 : ≥1% of TC or IC and <50% of TC and <10% of IC) PDL1 (TC1/2/3 or IC1/2/3 : ≥1% of TC or IC) PDL1 (TC3 or IC3 : ≥50% of TC or ≥10% of IC ) smoker (current or former) smoker (never)
Top evidence (RCT only, high risk of bias excluded)
Best available evidence (possibly low or very low)
All RCTs
All studies (RCT+OBS)
studies
metastatic/advanced NSCLC (mNSCLC) - 1st line (L1), nivolumab plus ipilimumab vs. all, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.79 [0.65; 0.96]
CheckMate 9LA, 2021 0.69 [0.55; 0.87]
0.75 [0.64 ; 0.87 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 9LA, 2021 2 0% 1,512 moderate not evaluable deaths (OS) (extension)detailed results CheckMate 9LA, 2021 0.66 [0.55; 0.80]
0.66 [0.55 ; 0.80 ] CheckMate 9LA, 2021 1 0% 719 NA not evaluable PFS (extension)detailed results CheckMate 9LA, 2021 0.68 [0.57; 0.82]
0.68 [0.57 ; 0.82 ] CheckMate 9LA, 2021 1 0% 719 NA not evaluable progression or deaths (PFS)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.82 [0.69; 0.97]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 0.58 [0.41; 0.82]
CheckMate 9LA, 2021 0.70 [0.57; 0.86]
0.72 [0.61 ; 0.86 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 44% 1,811 moderate not evaluable objective responses (ORR)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 1.31 [0.97; 1.76]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 2.26 [1.39; 3.66]
CheckMate 9LA, 2021 1.80 [1.31; 2.48]
1.68 [1.24 ; 2.26 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 53% 1,811 moderate not evaluable STRAE (any grade)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 1.96 [1.36; 2.83]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 2.67 [1.51; 4.74]
CheckMate 9LA, 2021 1.94 [1.36; 2.76]
2.05 [1.63 ; 2.59 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable STRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 1.98 [1.32; 2.98]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 2.19 [1.14; 4.20]
CheckMate 9LA, 2021 1.95 [1.33; 2.84]
2.00 [1.55 ; 2.58 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable TRAE (any grade)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.66 [0.46; 0.94]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 1.28 [0.71; 2.30]
CheckMate 9LA, 2021 1.55 [0.94; 2.55]
1.06 [0.60 ; 1.89 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 77% 1,779 moderate not evaluable TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.96 [0.72; 1.29]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 1.02 [0.64; 1.65]
CheckMate 9LA, 2021 1.44 [1.06; 1.94]
1.14 [0.87 ; 1.49 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 47% 1,779 moderate not evaluable TRAE leading to death (grade 5)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.99 [0.28; 3.45]
CheckMate 9LA, 2021 1.14 [0.38; 3.43]
1.07 [0.47 ; 2.45 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 9LA, 2021 2 0% 1,485 moderate not evaluable TRAE leading to discontinuation (any grade)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 3.13 [1.95; 5.03]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 3.49 [1.78; 6.83]
CheckMate 9LA, 2021 3.18 [1.94; 5.19]
3.22 [2.38 ; 4.36 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable TRAE leading to discontinuation (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 5.13 [2.63; 10.00]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 2.90 [1.32; 6.37]
CheckMate 9LA, 2021 3.48 [2.00; 6.05]
3.77 [2.59 ; 5.49 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable Adrenal insufficiency TRAE (grade 3-4)detailed results CheckMate 9LA, 2021 7.88 [0.41; 149.53]
7.88 [0.41 ; 149.53 ] CheckMate 9LA, 2021 1 0% 707 NA not evaluable Anaemia TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.11 [0.04; 0.28]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 0.26 [0.07; 0.92]
CheckMate 9LA, 2021 0.37 [0.22; 0.63]
0.23 [0.10 ; 0.52 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 60% 1,779 moderate not evaluable Asthenia TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 1.24 [0.33; 4.65]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 1.18 [0.23; 5.95]
CheckMate 9LA, 2021 0.36 [0.09; 1.37]
0.78 [0.34 ; 1.75 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 1% 1,779 moderate not evaluable Colitis TRAE (grade 3-4)detailed results CheckMate 9LA, 2021 9.87 [0.54; 181.39]
9.87 [0.54 ; 181.39 ] CheckMate 9LA, 2021 1 0% 707 NA not evaluable Constipation TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.99 [0.02; 50.01]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 0.59 [0.02; 17.65]
CheckMate 9LA, 2021 0.97 [0.02; 49.27]
0.80 [0.09 ; 6.87 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable Decreased appetite TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.99 [0.25; 3.99]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 0.29 [0.03; 2.62]
CheckMate 9LA, 2021 0.97 [0.24; 3.93]
0.80 [0.33 ; 1.97 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable Diarrhoea TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 3.00 [0.60; 14.96]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 1.78 [0.29; 10.84]
CheckMate 9LA, 2021 7.06 [1.59; 31.30]
3.66 [1.44 ; 9.30 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable Fatigue TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 2.00 [0.60; 6.70]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 0.29 [0.03; 2.62]
CheckMate 9LA, 2021 3.97 [0.84; 18.81]
1.64 [0.47 ; 5.72 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 45% 1,779 moderate not evaluable Febrile neutropenia TRAE (grade 3-4)detailed results CheckMate 9LA, 2021 1.38 [0.60; 3.15]
1.38 [0.60 ; 3.15 ] CheckMate 9LA, 2021 1 0% 707 NA not evaluable Hypothyroidism TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 1.18 [0.02; 59.79]
CheckMate 9LA, 2021 1.95 [0.07; 58.39]
1.57 [0.12 ; 20.54 ] CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 2 0% 1,001 moderate not evaluable Increased ALT TRAE (grade 3-4)detailed results CheckMate 9LA, 2021 2.46 [0.47; 12.75]
2.46 [0.47 ; 12.75 ] CheckMate 9LA, 2021 1 0% 707 NA not evaluable Increased lipase level TRAE (grade 3-4)detailed results CheckMate 9LA, 2021 7.55 [2.24; 25.47]
7.55 [2.24 ; 25.47 ] CheckMate 9LA, 2021 1 0% 707 NA not evaluable Maculopapular rash TRAE (grade 3-4)detailed results CheckMate 9LA, 2021 4.93 [0.57; 42.41]
4.93 [0.57 ; 42.41 ] CheckMate 9LA, 2021 1 0% 707 NA not evaluable Nausea TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.28 [0.06; 1.35]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 1.18 [0.16; 8.49]
CheckMate 9LA, 2021 1.63 [0.39; 6.89]
0.81 [0.26 ; 2.48 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 29% 1,779 moderate not evaluable Neutropenia TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.01 [0.00; 0.23]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 0.03 [0.00; 0.46]
CheckMate 9LA, 2021 0.71 [0.41; 1.24]
0.08 [0.00 ; 1.53 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 83% 1,779 moderate not evaluable Pruritus TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 3.97 [0.18; 88.42]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 4.77 [0.21; 106.62]
CheckMate 9LA, 2021 5.89 [0.29; 118.02]
4.84 [0.82 ; 28.43 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable Rash TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 18.21 [1.05; 315.26]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 7.20 [0.36; 145.12]
CheckMate 9LA, 2021 11.88 [0.66; 213.53]
11.78 [2.19 ; 63.31 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 0% 1,779 moderate not evaluable Thrombocytopenia TRAE (grade 3-4)detailed results CheckMate 9LA, 2021 1.09 [0.44; 2.70]
1.09 [0.44 ; 2.70 ] CheckMate 9LA, 2021 1 0% 707 NA not evaluable Vomiting TRAE (grade 3-4)detailed results CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.10 [0.01; 0.76]
CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 0.19 [0.02; 1.60]
CheckMate 9LA, 2021 1.17 [0.35; 3.88]
0.34 [0.07 ; 1.74 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, CheckMate 9LA, 2021 3 61% 1,779 moderate not evaluable 0.0 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-11-01 00:24 +01:00
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: 196,36,228,174,171,173,307,165,163,176,308,164,166,220
- treatments: 416,864