All patients
Age < 65y (younger) Age > 65y Age > 75y (older) Asian type cancer type (metastatic) cancer type (recurrent) cell type, non squamous cell cell type, squamous cell ECOG 0 ECOG 1 EGFR mutant 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 (TC2/3 or IC2/3 : ≥5% of TC or IC) PDL1 (TC3 or IC3 : ≥50% of TC or ≥10% of IC ) PDL1 (TPS >50%) smoker (current or former) smoker (Current) smoker (Former) smoker (never) stage III (locally advanced) stage IV (metastatic) Teff high Teff low
Top evidence (RCT only, high risk of bias excluded)
Best available evidence (possibly low or very low)
All RCTs
All studies (RCT+OBS)
metastatic/advanced NSCLC (mNSCLC) - 1st line (L1), immune chekpoint inhibitors vs. pemetrexed plus platin, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 0.78 [0.60; 1.02]
CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.79 [0.65; 0.96]
KEYNOTE-021, 2016 0.90 [0.42; 1.92]
0.79 [0.68 ; 0.92 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, KEYNOTE-021, 2016 3 0% 1,279 moderate not evaluable deaths (OS) (extension)detailed results KEYNOTE-021, 2016 0.71 [0.45; 1.12]
0.71 [0.45 ; 1.12 ] KEYNOTE-021, 2016 1 0% 123 NA not evaluable PFS (extension)detailed results KEYNOTE-021, 2016 0.54 [0.35; 0.83]
0.54 [0.35 ; 0.83 ] KEYNOTE-021, 2016 1 0% 123 NA not evaluable progression or deaths (PFS)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 0.73 [0.56; 0.95]
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]
KEYNOTE-021, 2016 0.53 [0.31; 0.91]
0.71 [0.59 ; 0.85 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 37% 1,578 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]
KEYNOTE-021, 2016 3.06 [1.45; 6.45]
1.93 [1.16 ; 3.20 ] CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 3 70% 1,215 moderate not evaluable objective responses (ORR) (extension)detailed results KEYNOTE-021, 2016 2.80 [1.34; 5.83]
2.80 [1.34 ; 5.83 ] KEYNOTE-021, 2016 1 0% 123 NA not evaluable STRAE (any grade)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.75 [1.00; 3.09]
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]
KEYNOTE-021, 2016 3.47 [1.25; 9.62]
2.12 [1.63 ; 2.76 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable STRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 2.05 [1.12; 3.76]
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]
KEYNOTE-021, 2016 5.56 [1.49; 20.67]
2.14 [1.60 ; 2.87 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable TRAE (any grade)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 3.42 [1.76; 6.65]
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]
KEYNOTE-021, 2016 0.95 [0.29; 3.12]
1.28 [0.58 ; 2.81 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 84% 1,548 moderate not evaluable TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 2.35 [1.53; 3.60]
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]
KEYNOTE-021, 2016 2.04 [0.92; 4.52]
1.42 [0.87 ; 2.31 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 78% 1,548 moderate not evaluable TRAE leading to death (grade 5)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 4.33 [0.48; 39.16]
CheckMate 227 (NI vs C ; PDL1>1%), 2018 0.99 [0.28; 3.45]
KEYNOTE-021, 2016 0.52 [0.05; 5.86]
1.20 [0.44 ; 3.23 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, KEYNOTE-021, 2016 3 0% 1,254 moderate not evaluable TRAE leading to discontinuation (any grade)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 0.89 [0.48; 1.63]
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]
KEYNOTE-021, 2016 0.76 [0.25; 2.35]
1.76 [0.82 ; 3.79 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 81% 1,548 moderate not evaluable TRAE leading to discontinuation (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 0.80 [0.38; 1.70]
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]
KEYNOTE-021, 2016 4.44 [0.48; 40.91]
2.50 [0.95 ; 6.59 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 78% 1,548 moderate not evaluable Acute kidney injury TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 4.32 [0.19; 97.73]
4.32 [0.19 ; 97.73 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Alopecia TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.05 [0.02 ; 53.86 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Anaemia TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.34 [0.75; 2.38]
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]
KEYNOTE-021, 2016 0.79 [0.27; 2.29]
0.43 [0.12 ; 1.49 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 86% 1,548 moderate not evaluable Asthenia TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.06 [0.07; 17.15]
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]
1.20 [0.46 ; 3.13 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018 3 0% 1,427 moderate not evaluable Blood creatinine increased TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.05 [0.02 ; 53.86 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Constipation TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 0.26 [0.01; 5.89]
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]
KEYNOTE-021, 2016 1.05 [0.02; 53.86]
0.57 [0.10 ; 3.32 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable Decreased appetite TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.43 [0.32; 6.48]
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]
KEYNOTE-021, 2016 1.05 [0.02; 53.86]
0.92 [0.37 ; 2.27 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable Diarrhoea TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.06 [0.15; 7.64]
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]
KEYNOTE-021, 2016 0.52 [0.02; 15.84]
1.72 [0.65 ; 4.59 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable Dizziness TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.05 [0.02 ; 53.86 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Dysgeusia TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.05 [0.02 ; 53.86 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Fatigue TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 2.18 [0.65; 7.39]
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]
KEYNOTE-021, 2016 4.32 [0.19; 97.73]
1.70 [0.78 ; 3.74 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 2% 1,548 moderate not evaluable Febrile neutropenia TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 2.12 [0.07; 64.42]
2.12 [0.07 ; 64.42 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.05 [0.02 ; 53.86 ] KEYNOTE-021, 2016 1 0% 121 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]
KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.11 [0.07 ; 17.94 ] CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 2 0% 415 moderate not evaluable Increase AST TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.06; 17.21]
1.05 [0.06 ; 17.21 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Increased ALT TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.06; 17.21]
1.05 [0.06 ; 17.21 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Increased lacrimation (TRAE grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.05 [0.02 ; 53.86 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Infusion-related reactions TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 2.12 [0.07; 64.42]
2.12 [0.07 ; 64.42 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Leucopenia TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 2.12 [0.07; 64.42]
2.12 [0.07 ; 64.42 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Nausea TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 0.85 [0.22; 3.21]
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]
KEYNOTE-021, 2016 2.12 [0.07; 64.42]
0.68 [0.28 ; 1.64 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable Neutropenia TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.19 [0.63; 2.24]
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]
KEYNOTE-021, 2016 2.14 [0.19; 24.25]
0.22 [0.02 ; 2.28 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 81% 1,548 moderate not evaluable Pancytopenia TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 0.52 [0.02; 15.84]
0.52 [0.02 ; 15.84 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Peripheral oedema TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.02; 53.86]
1.05 [0.02 ; 53.86 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Pneumonia TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 2.12 [0.07; 64.42]
2.12 [0.07 ; 64.42 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Pneumonitis TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 2.12 [0.07; 64.42]
2.12 [0.07 ; 64.42 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Pruritus TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.06 [0.02; 53.93]
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]
KEYNOTE-021, 2016 1.05 [0.02; 53.86]
2.53 [0.45 ; 14.15 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable Rash TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 2.13 [0.07; 64.04]
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]
KEYNOTE-021, 2016 2.12 [0.07; 64.42]
5.69 [1.18 ; 27.31 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 0% 1,548 moderate not evaluable Sepsis TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 2.12 [0.07; 64.42]
2.12 [0.07 ; 64.42 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Severe skin reaction TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.06; 17.21]
1.05 [0.06 ; 17.21 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Stomatitis TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 0.52 [0.02; 15.84]
0.52 [0.02 ; 15.84 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Thrombocytopenia TRAE (grade 3-4)detailed results KEYNOTE-021, 2016 1.05 [0.14; 7.73]
1.05 [0.14 ; 7.73 ] KEYNOTE-021, 2016 1 0% 121 NA not evaluable Vomiting TRAE (grade 3-4)detailed results CheckMate 227 (NC vs C ; PDL1<1%), 2018 1.43 [0.32; 6.48]
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]
KEYNOTE-021, 2016 2.12 [0.07; 64.42]
0.45 [0.10 ; 1.97 ] CheckMate 227 (NC vs C ; PDL1<1%), 2018, CheckMate 227 (NI vs C ; PDL1>1%), 2018, CheckMate 227 (NI vs C ; TMB >10 Mb), 2018, KEYNOTE-021, 2016 4 48% 1,548 moderate not evaluable 0.0 10.0 1.0 relative treatment effect www.metaEvidence.org 2024-06-29 13:03 +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: 196,36,228,174,171,173,307,165,163,176,308,164,166,220
- treatments: 204,504,850,329,558,579,549,868,502,741,556,812,813,367,851,361,602,1070,671,865,744,696,1083,1281,1282,1283,1082,866,852,417,603,1051,876,853,1018,661,673,1049,1440,854,374,1073,953,672,1080,862,855,360,719,721,720,842,642,674,1085,863,503,847,982,359,575,577,576,869,1081,981,875,505,952,1021,1079,767,1071,1074,873,561,644,1251,1044,724,874,1043,1041,1042,940,1258,746,745,856,634,861,416,864,769,980,369,743
