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mGC or mGEJC - 1st line (L1), pembrolizumab based treatment , 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) 0.88 [0.77, 1.01]< 10%2 studies (2/-)96.7 %lownot evaluable highcrucial-
progression or deaths (PFS) 1.18 [0.61, 2.30]< 196%2 studies (2/-)31.3 %lownot evaluable highimportant-
objective responses (ORR) 0.69 [0.13, 3.62]> 197%2 studies (2/-)33.0 %lownot evaluable highnon important-

safety endpoints 00

AE (any grade) 0.46 [0.20, 1.08]< 10%2 studies (2/-)96.3 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 0.32 [0.03, 4.02]< 199%2 studies (2/-)80.9 %lownot evaluable highnon important-
AE leading to death (grade 5) 1.29 [0.44, 3.78]< 10%2 studies (2/-)32.0 %lownot evaluable highnon important-
AE leading to treatment discontinuation (any grade) 0.58 [0.07, 5.15]< 196%2 studies (2/-)68.7 %lownot evaluable highnon important-
TRAE (any grade) 0.38 [0.03, 4.77]< 197%2 studies (2/-)77.1 %some concernnot evaluable moderatenon important-

TRAE (grade 3-4) endpoints 00

Alopecia TRAE (grade 3-4) 0.97 [0.06, 15.52]< 10%2 studies (2/-)50.9 %some concernnot evaluable moderatenon important-
Anaemia TRAE (grade 3-4) 0.29 [0.04, 2.39]< 192%2 studies (2/-)87.3 %lownot evaluable highnon important-
Asthenia TRAE (grade 3-4) 0.35 [0.04, 3.02]< 174%2 studies (2/-)83.0 %lownot evaluable highnon important-
Blood creatinine increased TRAE (grade 3-4) 0.73 [0.09, 6.29]< 10%2 studies (2/-)61.1 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.97 [0.06, 15.52]< 10%2 studies (2/-)50.9 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 0.34 [0.09, 1.27]< 169%2 studies (2/-)94.5 %lownot evaluable highnon important-
Diarrhoea TRAE (grade 3-4) 0.44 [0.11, 1.78]< 172%2 studies (2/-)87.4 %lownot evaluable highnon important-
Dizziness TRAE (grade 3-4) 0.73 [0.09, 6.31]< 10%2 studies (2/-)61.0 %lownot evaluable highnon important-
Dry skin TRAE (grade 3-4) 0.97 [0.06, 15.52]< 10%2 studies (2/-)50.9 %some concernnot evaluable moderatenon important-
Dysgeusia TRAE (grade 3-4) 0.97 [0.06, 15.52]< 10%2 studies (2/-)50.9 %some concernnot evaluable moderatenon important-
Fatigue TRAE (grade 3-4) 0.35 [0.02, 6.67]< 187%2 studies (2/-)75.6 %lownot evaluable highnon important-
Hypothyroidism TRAE (grade 3-4) 1.94 [0.18, 21.47]< 10%2 studies (2/-)29.6 %some concernnot evaluable moderatenon important-
Leucopenia TRAE (grade 3-4) 2.43 [0.23, 25.98]< 134%2 studies (2/-)23.2 %lownot evaluable highnon important-
Mucosal inflammation TRAE (grade 3-4) 0.20 [0.01, 4.07]< 177%2 studies (2/-)85.1 %lownot evaluable highnon important-
Nausea TRAE (grade 3-4) 0.26 [0.01, 5.10]< 187%2 studies (2/-)80.8 %lownot evaluable highnon important-
Neutropenia TRAE (grade 3-4) 0.08 [0.00, 12.29]< 192%2 studies (2/-)82.9 %lownot evaluable highnon important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 0.40 [0.02, 8.98]< 178%2 studies (2/-)71.7 %lownot evaluable highnon important-
Peripheral neuropathy TRAE (grade 3-4) 1.04 [0.16, 6.94]< 127%2 studies (2/-)48.5 %lownot evaluable highnon important-
Peripheral sensory neuropathy TRAE (grade 3-4) 5.91 [0.29, 118.71]< 10%1 study (1/-)12.5 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 0.97 [0.06, 15.52]< 10%2 studies (2/-)50.9 %some concernnot evaluable moderatenon important-
Rash TRAE (grade 3-4) 1.44 [0.11, 18.83]< 10%2 studies (2/-)39.1 %lownot evaluable highnon important-
Stomatitis TRAE (grade 3-4) 0.34 [0.02, 6.97]< 177%2 studies (2/-)75.7 %lownot evaluable highnon important-
Thrombocytopenia TRAE (grade 3-4) 0.42 [0.03, 5.35]< 165%2 studies (2/-)74.5 %lownot evaluable highnon important-
Vomiting TRAE (grade 3-4) 0.22 [0.01, 5.00]< 179%2 studies (2/-)82.6 %lownot evaluable highnon important-
Weight decreased TRAE (grade 3-4) 1.22 [0.17, 8.73]< 10%2 studies (2/-)42.0 %lownot evaluable highnon 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.