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mCRC - 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

progression or deaths (PFS) 0.60 [0.45, 0.80]< 10%1 study (1/-)100.0 %NAnot evaluable important-
objective responses (ORR) 1.57 [0.99, 2.50]> 10%1 study (1/-)97.2 %NAnot evaluable non important-

safety endpoints 00

AE (any grade) 0.26 [0.03, 2.38]< 10%1 study (1/-)88.2 %NAnot evaluable non important-
AE (grade 3-4) 0.41 [0.25, 0.67]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
AE leading to death (grade 5) 0.79 [0.26, 2.42]< 10%1 study (1/-)65.8 %NAnot evaluable non important-
TRAE (grade 3-4) 0.14 [0.08, 0.23]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
TRAE leading to death (grade 5) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 3.77 [0.17, 84.42]< 10%1 study (1/-)20.4 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.26 [0.05, 1.26]< 10%1 study (1/-)95.2 %NAnot evaluable non important-
Arthralgia TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.09 [0.00, 1.67]< 10%1 study (1/-)94.5 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 9.63 [0.52, 177.85]< 10%1 study (1/-)6.6 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 0.15 [0.01, 3.08]< 10%1 study (1/-)88.7 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 1.88 [0.06, 56.32]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 0.18 [0.05, 0.66]< 10%1 study (1/-)99.5 %NAnot evaluable non important-
Dizziness TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Epistaxis TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.20 [0.06, 0.72]< 10%1 study (1/-)99.3 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 7.65 [0.40, 146.03]< 10%1 study (1/-)9.1 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Hypophysitis TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 1.88 [0.17, 20.97]< 10%1 study (1/-)30.5 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 2.84 [0.29, 27.62]< 10%1 study (1/-)18.6 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 0.07 [0.00, 1.35]< 10%1 study (1/-)95.9 %NAnot evaluable non important-
Mucosal inflammation TRAE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.15 [0.01, 3.08]< 10%1 study (1/-)88.7 %NAnot evaluable non important-
Nephritis TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.02 [0.00, 0.30]< 10%1 study (1/-)99.7 %NAnot evaluable non important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Pancreatitis TRAE (grade 3-4) 1.88 [0.06, 56.32]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Peripheral sensory neuropathy TRAE (grade 3-4) 0.15 [0.01, 3.08]< 10%1 study (1/-)88.7 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 0.93 [0.06, 15.08]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Severe skin reaction TRAE (grade 3-4) 0.93 [0.13, 6.72]< 10%1 study (1/-)52.7 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 0.07 [0.00, 1.35]< 10%1 study (1/-)95.9 %NAnot evaluable non important-
Thyroiditis TRAE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.09 [0.00, 1.67]< 10%1 study (1/-)94.5 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Abdominal pain AE (grade 3-4) 0.93 [0.34, 2.55]< 10%1 study (1/-)55.5 %NAnot evaluable non important-
Alopecia AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Anaemia AE (grade 3-4) 0.47 [0.19, 1.15]< 10%1 study (1/-)95.1 %NAnot evaluable non important-
Arthralgia AE (grade 3-4) 1.88 [0.06, 56.32]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 0.46 [0.11, 1.86]< 10%1 study (1/-)86.2 %NAnot evaluable non important-
Back pain AE (grade 3-4) 1.88 [0.17, 20.97]< 10%1 study (1/-)30.5 %NAnot evaluable non important-
Constipation AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Cough AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Decreased appetite AE (grade 3-4) 0.06 [0.00, 1.13]< 10%1 study (1/-)96.8 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 0.50 [0.21, 1.16]< 10%1 study (1/-)94.7 %NAnot evaluable non important-
Dizziness AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Dry skin AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Dyspepsia AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 1.88 [0.06, 56.32]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Epistaxis AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.41 [0.15, 1.10]< 10%1 study (1/-)96.1 %NAnot evaluable non important-
Headache AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Hypertension AE (grade 3-4) 1.51 [0.57, 4.00]< 10%1 study (1/-)20.6 %NAnot evaluable non important-
Hypothyroidism AE (grade 3-4) 0.93 [0.02, 47.41]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Increase AST AE (grade 3-4) 1.25 [0.28, 5.70]< 10%1 study (1/-)38.6 %NAnot evaluable non important-
Increased ALT AE (grade 3-4) 1.25 [0.28, 5.70]< 10%1 study (1/-)38.6 %NAnot evaluable non important-
Mucosal inflammation AE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Nausea AE (grade 3-4) 0.61 [0.17, 2.22]< 10%1 study (1/-)77.2 %NAnot evaluable non important-
Neutropenia AE (grade 3-4) 0.02 [0.00, 0.30]< 10%1 study (1/-)99.7 %NAnot evaluable non important-
Palmar–plantar erythrodysesthesia syndrome AE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Peripheral neuropathy AE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Peripheral oedema AE (grade 3-4) 0.23 [0.01, 5.17]< 10%1 study (1/-)81.9 %NAnot evaluable non important-
Peripheral sensory neuropathy AE (grade 3-4) 0.15 [0.01, 3.08]< 10%1 study (1/-)88.7 %NAnot evaluable non important-
Pruritus AE (grade 3-4) 0.47 [0.02, 13.99]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 1.88 [0.06, 56.32]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Rash AE (grade 3-4) 0.93 [0.06, 15.08]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Stomatitis AE (grade 3-4) 0.07 [0.00, 1.35]< 10%1 study (1/-)95.9 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 0.26 [0.05, 1.26]< 10%1 study (1/-)95.2 %NAnot evaluable non important-
Weight decreased AE (grade 3-4) 0.93 [0.06, 15.08]< 10%1 study (1/-)51.9 %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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