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melanoma (ML), atezolizumab plus cometinib , 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) 1.06 [0.69, 1.62]< 10%1 study (1/-)39.4 %NAnot evaluable crucial-
progression or deaths (PFS) 1.15 [0.88, 1.50]< 10%1 study (1/-)15.2 %NAnot evaluable important-
DCR 0.91 [0.63, 1.32]> 10%1 study (1/-)31.6 %NAnot evaluable non important-
objective responses (ORR) 0.77 [0.50, 1.17]> 10%1 study (1/-)10.9 %NAnot evaluable non important-

safety endpoints 00

AE (any grade) 14.27 [3.34, 61.03]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
AE (grade 3-4) 4.03 [2.70, 6.00]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
AE leading to death (grade 5) 1.39 [0.43, 4.44]< 10%1 study (1/-)29.1 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Abdominal pain AE (grade 3-4) 0.98 [0.14, 7.03]< 10%1 study (1/-)50.7 %NAnot evaluable non important-
Anaemia AE (grade 3-4) 1.74 [0.50, 6.04]< 10%1 study (1/-)19.1 %NAnot evaluable non important-
Arthralgia AE (grade 3-4) 0.98 [0.02, 49.71]< 10%1 study (1/-)50.4 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 1.74 [0.50, 6.04]< 10%1 study (1/-)19.1 %NAnot evaluable non important-
Constipation AE (grade 3-4) 0.98 [0.02, 49.71]< 10%1 study (1/-)50.4 %NAnot evaluable non important-
Decreased appetite AE (grade 3-4) 1.97 [0.07, 58.97]< 10%1 study (1/-)35.0 %NAnot evaluable non important-
Dermatitis acneiform AE (grade 3-4) 22.68 [1.32, 388.47]< 10%1 study (1/-)1.7 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 4.44 [1.47, 13.42]< 10%1 study (1/-)0.4 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 1.65 [0.39, 7.00]< 10%1 study (1/-)24.9 %NAnot evaluable non important-
Headache AE (grade 3-4) 1.97 [0.07, 58.97]< 10%1 study (1/-)35.0 %NAnot evaluable non important-
Hypertension AE (grade 3-4) 1.77 [0.73, 4.30]< 10%1 study (1/-)10.5 %NAnot evaluable non important-
Increase AST AE (grade 3-4) 3.00 [0.60, 15.03]< 10%1 study (1/-)9.1 %NAnot evaluable non important-
Increased ALT AE (grade 3-4) 1.99 [0.49, 8.06]< 10%1 study (1/-)16.8 %NAnot evaluable non important-
Increased Lipase Level AE (grade 3-4) 2.00 [0.59, 6.74]< 10%1 study (1/-)13.2 %NAnot evaluable non important-
Nausea AE (grade 3-4) 10.02 [0.54, 184.60]< 10%1 study (1/-)6.3 %NAnot evaluable non important-
Peripheral oedema AE (grade 3-4) 0.98 [0.06, 15.80]< 10%1 study (1/-)50.5 %NAnot evaluable non important-
Pruritus AE (grade 3-4) 0.98 [0.02, 49.71]< 10%1 study (1/-)50.4 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 6.03 [0.72, 50.50]< 10%1 study (1/-)5.0 %NAnot evaluable non important-
Rash AE (grade 3-4) 7.83 [1.77, 34.66]< 10%1 study (1/-)0.3 %NAnot evaluable non important-
Rash maculopapular AE (grade 3-4) 7.98 [0.42, 151.89]< 10%1 study (1/-)8.6 %NAnot evaluable non important-
Sepsis AE (grade 3-4) 12.08 [0.67, 217.70]< 10%1 study (1/-)4.7 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 2.49 [0.48, 12.97]< 10%1 study (1/-)14.0 %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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