All patients
Age < 65y (younger) Age > 65y cell type, non squamous cell cell type, squamous cell ECOG 0 ECOG 1 Gender, female Gender, male metastasis (brain) NO metastasis (brain) YES 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 ) PDL1 (TPS >50%) smoker (current or former) smoker (Current) smoker (Former) smoker (never) stage III (locally advanced) stage IV (metastatic)
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), pembrolizumab based treatment vs. placebo plus SoC, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results KEYNOTE-189, 2018 0.49 [0.38; 0.64]
KEYNOTE-407, 2018 0.64 [0.49; 0.84]
0.56 [0.43 ; 0.73 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 49% 1,175 low not evaluable deaths (OS) (extension)detailed results KEYNOTE-189, 2018 0.56 [0.45; 0.70]
0.56 [0.45 ; 0.70 ] KEYNOTE-189, 2018 1 0% 616 NA not evaluable PFS (extension)detailed results KEYNOTE-189, 2018 0.48 [0.40; 0.58]
0.48 [0.40 ; 0.58 ] KEYNOTE-189, 2018 1 0% 616 NA not evaluable progression or deaths (PFS)detailed results KEYNOTE-189, 2018 0.52 [0.43; 0.63]
KEYNOTE-407, 2018 0.56 [0.45; 0.70]
0.54 [0.46 ; 0.62 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,175 low not evaluable objective responses (ORR)detailed results KEYNOTE-189, 2018 3.88 [2.61; 5.79]
KEYNOTE-407, 2018 2.20 [1.57; 3.09]
2.90 [1.66 ; 5.04 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 78% 1,175 low not evaluable objective responses (ORR) (extension)detailed results KEYNOTE-189, 2018 3.84 [2.58; 5.70]
3.84 [2.58 ; 5.70 ] KEYNOTE-189, 2018 1 0% 616 NA not evaluable AE (any grade)detailed results KEYNOTE-189, 2018 4.04 [0.36; 44.82]
KEYNOTE-407, 2018 1.20 [0.36; 3.96]
1.52 [0.52 ; 4.45 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.03 [0.73; 1.45]
KEYNOTE-407, 2018 0.99 [0.70; 1.39]
1.01 [0.79 ; 1.28 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable AE leading to death (grade 5)detailed results KEYNOTE-189, 2018 1.13 [0.56; 2.28]
KEYNOTE-407, 2018 1.31 [0.69; 2.49]
1.23 [0.76 ; 1.97 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable AE leading to treatment discontinuation (any grade)detailed results KEYNOTE-189, 2018 2.19 [1.31; 3.65]
KEYNOTE-407, 2018 2.28 [1.45; 3.61]
2.24 [1.59 ; 3.15 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable AE leading to treatment discontinuation (grade 3-4)detailed results KEYNOTE-189, 2018 2.04 [1.16; 3.59]
KEYNOTE-407, 2018 2.09 [1.28; 3.39]
2.07 [1.43 ; 2.99 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable TRAE leading to death (grade 5)detailed results KEYNOTE-407, 2018 1.70 [0.61; 4.75]
1.70 [0.61 ; 4.75 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Adrenal insufficiency TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 0.50 [0.03; 8.00]
0.50 [0.03 ; 8.00 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Colitis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 3.01 [0.15; 60.33]
3.01 [0.15 ; 60.33 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Diabetes TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 1.00 [0.03; 29.86]
1.00 [0.03 ; 29.86 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Hepatitis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 4.02 [0.21; 76.41]
4.02 [0.21 ; 76.41 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Hyperthyroidism TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 0.50 [0.01; 25.20]
0.50 [0.01 ; 25.20 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Hypophysitis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 0.50 [0.01; 25.20]
0.50 [0.01 ; 25.20 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Hypothyroidism TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 2.00 [0.09; 44.56]
2.00 [0.09 ; 44.56 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Infusion-related reactions TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 1.00 [0.03; 29.86]
1.00 [0.03 ; 29.86 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Myositis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 0.50 [0.01; 25.20]
0.50 [0.01 ; 25.20 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Nephritis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 6.06 [0.34; 109.04]
6.06 [0.34 ; 109.04 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Pancreatitis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 2.00 [0.09; 44.56]
2.00 [0.09 ; 44.56 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Pneumonitis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 1.00 [0.30; 3.35]
1.00 [0.30 ; 3.35 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Severe skin reaction TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 1.00 [0.30; 3.35]
1.00 [0.30 ; 3.35 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Thyroiditis TRAE (grade 3-4)detailed results KEYNOTE-189, 2018 0.50 [0.01; 25.20]
0.50 [0.01 ; 25.20 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable hepatitis (Autoimmune) AE (grade 3-4)detailed results KEYNOTE-407, 2018 10.24 [0.56; 188.30]
10.24 [0.56 ; 188.30 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Alopecia AE (grade 3-4)detailed results KEYNOTE-407, 2018 0.33 [0.03; 3.22]
0.33 [0.03 ; 3.22 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Anaemia AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.07 [0.67; 1.71]
KEYNOTE-407, 2018 0.72 [0.46; 1.11]
0.87 [0.58 ; 1.29 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 36% 1,165 low not evaluable Arthralgia AE (grade 3-4)detailed results KEYNOTE-407, 2018 2.03 [0.37; 11.17]
2.03 [0.37 ; 11.17 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Asthenia AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.83 [0.78; 4.31]
KEYNOTE-407, 2018 0.60 [0.21; 1.66]
1.08 [0.36 ; 3.25 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 63% 1,165 low not evaluable Colitis AE (grade 3-4)detailed results KEYNOTE-407, 2018 2.04 [0.50; 8.23]
2.04 [0.50 ; 8.23 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Constipation AE (grade 3-4)detailed results KEYNOTE-189, 2018 2.00 [0.22; 18.06]
KEYNOTE-407, 2018 0.67 [0.11; 4.04]
1.04 [0.26 ; 4.17 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable Cough AE (grade 3-4)detailed results KEYNOTE-189, 2018 0.50 [0.01; 25.20]
KEYNOTE-407, 2018 0.67 [0.11; 4.04]
0.64 [0.12 ; 3.26 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable Decreased appetite AE (grade 3-4)detailed results KEYNOTE-189, 2018 3.02 [0.36; 25.28]
KEYNOTE-407, 2018 1.21 [0.37; 4.02]
1.51 [0.53 ; 4.30 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable Diarrhoea AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.79 [0.71; 4.50]
KEYNOTE-407, 2018 1.88 [0.69; 5.16]
1.83 [0.93 ; 3.61 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable Dyspnoea AE (grade 3-4)detailed results KEYNOTE-189, 2018 0.67 [0.30; 1.48]
KEYNOTE-407, 2018 3.04 [0.31; 29.44]
0.97 [0.27 ; 3.47 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 35% 1,165 low not evaluable Epistaxis AE (grade 3-4)detailed results KEYNOTE-407, 2018 1.01 [0.02; 50.94]
1.01 [0.02 ; 50.94 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Fatigue AE (grade 3-4)detailed results KEYNOTE-189, 2018 2.37 [0.89; 6.34]
KEYNOTE-407, 2018 0.82 [0.33; 2.01]
1.37 [0.48 ; 3.87 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 59% 1,165 low not evaluable Hyperthyroidism AE (grade 3-4)detailed results KEYNOTE-407, 2018 2.02 [0.07; 60.40]
2.02 [0.07 ; 60.40 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Hypophysitis AE (grade 3-4)detailed results KEYNOTE-407, 2018 4.05 [0.18; 90.23]
4.05 [0.18 ; 90.23 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Hypothyroidism AE (grade 3-4)detailed results KEYNOTE-407, 2018 2.02 [0.07; 60.40]
2.02 [0.07 ; 60.40 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Infusion-related reaction AE (grade 3-4)detailed results KEYNOTE-407, 2018 4.07 [0.45; 36.67]
4.07 [0.45 ; 36.67 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Lacrimation increased AE (grade 3-4)detailed results KEYNOTE-189, 2018 0.50 [0.01; 25.20]
0.50 [0.01 ; 25.20 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Myalgia AE (grade 3-4)detailed results KEYNOTE-407, 2018 2.02 [0.18; 22.43]
2.02 [0.18 ; 22.43 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Nausea AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.00 [0.40; 2.51]
KEYNOTE-407, 2018 0.75 [0.17; 3.39]
0.92 [0.42 ; 2.03 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable Neutropenia AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.39 [0.84; 2.30]
KEYNOTE-407, 2018 0.90 [0.61; 1.32]
1.08 [0.71 ; 1.66 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 46% 1,165 low not evaluable Peripheral neuropathy AE (grade 3-4)detailed results KEYNOTE-407, 2018 1.52 [0.25; 9.15]
1.52 [0.25 ; 9.15 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Peripheral oedema AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.00 [0.03; 29.86]
1.00 [0.03 ; 29.86 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Pneumonitis AE (grade 3-4)detailed results KEYNOTE-407, 2018 3.07 [0.61; 15.32]
3.07 [0.61 ; 15.32 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Pyrexia AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.00 [0.03; 29.86]
KEYNOTE-407, 2018 1.01 [0.14; 7.20]
1.00 [0.18 ; 5.51 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable Rash AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.17 [0.30; 4.56]
1.17 [0.30 ; 4.56 ] KEYNOTE-189, 2018 1 0% 607 NA not evaluable Severe skin reactions AE (grade 3-4)detailed results KEYNOTE-407, 2018 3.04 [0.31; 29.44]
3.04 [0.31 ; 29.44 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Thrombocytopenia AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.15 [0.60; 2.21]
KEYNOTE-407, 2018 1.07 [0.55; 2.08]
1.11 [0.70 ; 1.77 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 0% 1,165 low not evaluable Thyroiditis AE (grade 3-4)detailed results KEYNOTE-407, 2018 2.02 [0.07; 60.40]
2.02 [0.07 ; 60.40 ] KEYNOTE-407, 2018 1 0% 558 NA not evaluable Vomiting AE (grade 3-4)detailed results KEYNOTE-189, 2018 1.26 [0.48; 3.29]
KEYNOTE-407, 2018 0.16 [0.02; 1.38]
0.57 [0.08 ; 3.98 ] KEYNOTE-189, 2018, KEYNOTE-407, 2018 2 66% 1,165 low not evaluable 0.2 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-09-30 20:52 +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: 196,36,228,174,171,173,307,165,163,176,308,164,166,220
- treatments: 847,982,359,575,577,576,869,1081,981,875,505,952,1021,1079,767,1071,1074,873,561