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metastatic/advanced NSCLC (mNSCLC) - 1st line (L1), pembrolizumab and pemetrexed plus platin versus platinum association, meta-analysis of study results

Outcome Relative effect 95%CI LoD Trt. better when I2 k (RCT/OBS) Bayesian probability Overall ROB Publication bias Degree of certainty Endpoint importance Published MA

efficacy endpoints 00

deaths (OS) 0.90 [0.42, 1.92]< 10%1 study (1/-)60.7 %NAnot evaluable crucial-
deaths (OS) (extension) 0.71 [0.45, 1.12]< 10%1 study (1/-)92.9 %NAnot evaluable important-
PFS (extension) 0.54 [0.35, 0.83]< 10%1 study (1/-)99.7 %NAnot evaluable important-
progression or deaths (PFS) 0.53 [0.31, 0.91]< 10%1 study (1/-)99.0 %NAnot evaluable important-
objective responses (ORR) 3.06 [1.45, 6.45]> 10%1 study (1/-)99.8 %NAnot evaluable non important-
objective responses (ORR) (extension) 2.80 [1.34, 5.83]> 10%1 study (1/-)99.7 %NAnot evaluable non important-

safety endpoints 00

STRAE (any grade) 3.47 [1.25, 9.62]< 10%1 study (1/-)0.8 %NAnot evaluable non important-
STRAE (grade 3-4) 5.56 [1.49, 20.67]< 10%1 study (1/-)0.5 %NAnot evaluable non important-
TRAE (any grade) 0.95 [0.29, 3.12]< 10%1 study (1/-)53.6 %NAnot evaluable non important-
TRAE (grade 3-4) 2.04 [0.92, 4.52]< 10%1 study (1/-)4.0 %NAnot evaluable non important-
TRAE leading to death (grade 5) 0.52 [0.05, 5.86]< 10%1 study (1/-)70.1 %NAnot evaluable non important-
TRAE leading to discontinuation (any grade) 0.76 [0.25, 2.35]< 10%1 study (1/-)68.0 %NAnot evaluable non important-
TRAE leading to discontinuation (grade 3-4) 4.44 [0.48, 40.91]< 10%1 study (1/-)9.6 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Acute kidney injury TRAE (grade 3-4) 4.32 [0.19, 97.73]< 10%1 study (1/-)18.2 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.79 [0.27, 2.29]< 10%1 study (1/-)66.6 %NAnot evaluable non important-
Blood creatinine increased TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 0.52 [0.02, 15.84]< 10%1 study (1/-)64.4 %NAnot evaluable non important-
Dizziness TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Dysgeusia TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 4.32 [0.19, 97.73]< 10%1 study (1/-)18.2 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 1.05 [0.06, 17.21]< 10%1 study (1/-)48.6 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 1.05 [0.06, 17.21]< 10%1 study (1/-)48.6 %NAnot evaluable non important-
Increased lacrimation (TRAE grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 2.14 [0.19, 24.25]< 10%1 study (1/-)27.1 %NAnot evaluable non important-
Pancytopenia TRAE (grade 3-4) 0.52 [0.02, 15.84]< 10%1 study (1/-)64.4 %NAnot evaluable non important-
Peripheral oedema TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Pneumonia TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Sepsis TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Severe skin reaction TRAE (grade 3-4) 1.05 [0.06, 17.21]< 10%1 study (1/-)48.6 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 0.52 [0.02, 15.84]< 10%1 study (1/-)64.4 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 1.05 [0.14, 7.73]< 10%1 study (1/-)48.0 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-

LoD: level of statistical demonstration: Statistically conclusive: statistically significant with a strict control of overall risk of type 1 error (statistically demonstrated), does not take into account the risk of bias; suggested: nominally statistically significant but without a strict control of overall risk of type 1 error; inconclusive: not nominally statistically significant; safety concerns;
Bayesian probability: Bayesian posterior probability of treatment effect (computed with a noninformative prior); ROB: risk of bias; k: number of studies; published MA: number of published meta-analysis on the same topic; degree of certainty adapted from GRADE. Trt. better when: indicates when the relative treatment effect shows that the studied treatment is better than control.



 

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