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malignant mesothelioma (mMS) - 1st line (L1), immune chekpoint inhibitors , 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) 0.74 [0.60, 0.91]< 10%1 study (1/-)99.8 %NAnot evaluable crucial-
progression or deaths (PFS) 1.00 [0.82, 1.21]< 10%1 study (1/-)50.0 %NAnot evaluable important-
DCR 0.57 [0.38, 0.87]> 10%1 study (1/-)0.4 %NAnot evaluable non important-
objective responses (ORR) 0.88 [0.64, 1.22]> 10%1 study (1/-)21.8 %NAnot evaluable non important-

safety endpoints 00

STRAE (any grade) 0.92 [0.65, 1.31]< 10%1 study (1/-)67.2 %NAnot evaluable non important-
TRAE leading to death (grade 5) 2.86 [0.30, 27.64]< 10%1 study (1/-)18.4 %NAnot evaluable non important-
TRAE leading to discontinuation (any grade) 1.59 [1.05, 2.41]< 10%1 study (1/-)1.5 %NAnot evaluable non important-
TRAE leading to discontinuation (grade 3-4) 2.21 [1.28, 3.81]< 10%1 study (1/-)0.2 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Abdominal pain TRAE (grade 3-4) 0.47 [0.02, 14.14]< 10%1 study (1/-)66.5 %NAnot evaluable non important-
Acute kidney injury TRAE (grade 3-4) 7.66 [0.40, 145.59]< 10%1 study (1/-)9.0 %NAnot evaluable non important-
Adrenal insufficiency TRAE (grade 3-4) 1.90 [0.06, 56.75]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.03 [0.00, 0.19]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Arthralgia TRAE (grade 3-4) 1.90 [0.06, 56.75]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Arthritis TRAE (grade 3-4) 3.81 [0.17, 84.75]< 10%1 study (1/-)20.2 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.04 [0.00, 0.64]< 10%1 study (1/-)98.8 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 6.76 [0.83, 55.31]< 10%1 study (1/-)3.8 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 0.47 [0.02, 14.14]< 10%1 study (1/-)66.5 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 0.95 [0.13, 6.76]< 10%1 study (1/-)52.2 %NAnot evaluable non important-
Dermatitis acneiform TRAE (grade 3-4) 1.90 [0.06, 56.75]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 4.86 [1.06, 22.39]< 10%1 study (1/-)2.1 %NAnot evaluable non important-
Dyspnoea TRAE (grade 3-4) 0.47 [0.02, 14.14]< 10%1 study (1/-)66.5 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.56 [0.13, 2.38]< 10%1 study (1/-)78.2 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 0.16 [0.01, 3.14]< 10%1 study (1/-)88.5 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 3.81 [0.17, 84.75]< 10%1 study (1/-)20.2 %NAnot evaluable non important-
Hypersensitivity TRAE (grade 3-4) 1.90 [0.06, 56.75]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 0.95 [0.02, 47.87]< 10%1 study (1/-)51.1 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 5.73 [0.29, 114.85]< 10%1 study (1/-)13.0 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 9.61 [0.52, 176.72]< 10%1 study (1/-)6.6 %NAnot evaluable non important-
Increased lipase level TRAE (grade 3-4) 11.79 [1.52, 91.29]< 10%1 study (1/-)0.9 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 5.73 [0.29, 114.85]< 10%1 study (1/-)13.0 %NAnot evaluable non important-
Maculopapular rash TRAE (grade 3-4) 1.90 [0.06, 56.75]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Mucosal inflammation TRAE (grade 3-4) 0.24 [0.01, 5.24]< 10%1 study (1/-)81.7 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 1.90 [0.06, 56.75]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 3.81 [0.17, 84.75]< 10%1 study (1/-)20.2 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.13 [0.02, 1.08]< 10%1 study (1/-)97.0 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.04 [0.01, 0.16]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Pancytopenia TRAE (grade 3-4) 0.09 [0.01, 1.71]< 10%1 study (1/-)94.3 %NAnot evaluable non important-
Pneumonia TRAE (grade 3-4) 0.47 [0.02, 14.14]< 10%1 study (1/-)66.5 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 1.90 [0.06, 56.75]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 5.73 [0.29, 114.85]< 10%1 study (1/-)13.0 %NAnot evaluable non important-
Pyrexia TRAE (grade 3-4) 0.47 [0.02, 14.14]< 10%1 study (1/-)66.5 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 5.73 [0.29, 114.85]< 10%1 study (1/-)13.0 %NAnot evaluable non important-
Sepsis TRAE (grade 3-4) 0.47 [0.02, 14.14]< 10%1 study (1/-)66.5 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 0.47 [0.02, 14.14]< 10%1 study (1/-)66.5 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 0.18 [0.04, 0.85]< 10%1 study (1/-)98.5 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.08 [0.00, 1.39]< 10%1 study (1/-)95.7 %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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