All patients
Age < 65y (younger) Age > 65y 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 (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), pembrolizumab plus SoC 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 2024-10-01 08:14 +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: 873