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mGC or mGEJC - L1 - HER2 negative, anti-PD-(L)1 , 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) 0.80 [0.68, 0.94]< 10%1 study (1/-)99.7 %NAnot evaluable crucial-
progression or deaths (PFS) 0.77 [0.68, 0.87]< 10%1 study (1/-)100.0 %NAnot evaluable important-
objective responses (ORR) 1.63 [1.30, 2.04]> 10%1 study (1/-)100.0 %NAnot evaluable non important-

safety endpoints 00

STRAE (any grade) 1.98 [1.50, 2.61]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
STRAE (grade 3-4) 1.80 [1.33, 2.44]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
TRAE (any grade) 2.17 [1.49, 3.17]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
TRAE (grade 3-4) 1.80 [1.47, 2.21]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
TRAE leading to death (grade 5) 7.88 [0.42, 149.34]< 10%1 study (1/-)8.7 %NAnot evaluable non important-
TRAE leading to discontinuation (any grade) 1.85 [1.48, 2.30]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
TRAE leading to discontinuation (grade 3-4) 2.12 [1.55, 2.90]< 10%1 study (1/-)0.0 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Anaemia TRAE (grade 3-4) 2.27 [1.34, 3.84]< 10%1 study (1/-)0.1 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.68 [0.26, 1.81]< 10%1 study (1/-)77.8 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 1.06 [0.49, 2.26]< 10%1 study (1/-)44.3 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 1.45 [0.85, 2.46]< 10%1 study (1/-)8.4 %NAnot evaluable non important-
Endocrine disorders TRAE (grade 3-4) 9.86 [0.54, 180.88]< 10%1 study (1/-)6.4 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 1.76 [0.96, 3.22]< 10%1 study (1/-)3.3 %NAnot evaluable non important-
Gastrointestinal disorders TRAE (grade 3-4) 1.73 [1.04, 2.86]< 10%1 study (1/-)1.7 %NAnot evaluable non important-
Hepatobiliary disorders TRAE (grade 3-4) 1.81 [0.97, 3.36]< 10%1 study (1/-)3.0 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 2.38 [0.83, 6.77]< 10%1 study (1/-)5.3 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 1.18 [0.36, 3.88]< 10%1 study (1/-)39.4 %NAnot evaluable non important-
Increased lipase level TRAE (grade 3-4) 2.87 [1.61, 5.12]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 1.03 [0.55, 1.95]< 10%1 study (1/-)46.0 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 1.29 [0.96, 1.72]< 10%1 study (1/-)4.5 %NAnot evaluable non important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 1.81 [0.67, 4.92]< 10%1 study (1/-)12.3 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 1.40 [0.80, 2.44]< 10%1 study (1/-)11.9 %NAnot evaluable non important-
Peripheral sensory neuropathy TRAE (grade 3-4) 1.12 [0.54, 2.32]< 10%1 study (1/-)37.6 %NAnot evaluable non important-
Renal and urinary disorders TRAE (grade 3-4) 5.92 [0.71, 49.31]< 10%1 study (1/-)5.1 %NAnot evaluable non important-
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) 13.96 [1.83, 106.45]< 10%1 study (1/-)0.6 %NAnot evaluable non important-
Skin and subcutaneous tissue disorders TRAE (grade 3-4) 4.36 [1.79, 10.66]< 10%1 study (1/-)0.1 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 1.44 [0.71, 2.95]< 10%1 study (1/-)15.6 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.69 [0.37, 1.29]< 10%1 study (1/-)87.8 %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.