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metastatic/advanced mGC or mGEJC, anti-PD-(L)1 versus Standard of Care (SoC), 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) 0.86 [0.78, 0.94]< 10%4 studies (4/-)99.9 %some concernnot evaluable moderatecrucial-
progression or deaths (PFS) 1.02 [0.73, 1.44]< 193%4 studies (4/-)44.5 %some concernnot evaluable moderateimportant-
DCR 0.62 [0.43, 0.89]> 10%1 study (1/-)0.5 %NAnot evaluable non important-
objective responses (ORR) 0.92 [0.44, 1.95]> 194%4 studies (4/-)41.9 %some concernnot evaluable moderatenon important-

safety endpoints 00

AE (any grade) 0.74 [0.33, 1.67]< 151%3 studies (3/-)76.5 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 0.47 [0.10, 2.17]< 198%3 studies (3/-)83.4 %some concernnot evaluable moderatenon important-
AE leading to death (grade 5) 1.24 [0.67, 2.31]< 10%3 studies (3/-)24.5 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 0.53 [0.16, 1.78]< 194%3 studies (3/-)84.7 %some concernnot evaluable moderatenon important-
SAE (any grade) 1.26 [0.86, 1.83]< 10%1 study (1/-)11.9 %NAnot evaluable non important-
STRAE (any grade) 1.31 [0.54, 3.21]< 185%2 studies (2/-)27.5 %some concernnot evaluable moderatenon important-
STRAE (grade 3-4) 1.80 [1.33, 2.44]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
TRAE (any grade) 0.62 [0.17, 2.32]< 197%4 studies (4/-)76.0 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.75 [0.13, 4.28]< 198%2 studies (2/-)62.5 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 2.25 [0.15, 33.86]< 132%2 studies (2/-)28.1 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.76 [0.13, 4.44]< 198%2 studies (2/-)61.8 %some concernnot evaluable moderatenon 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

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) 0.61 [0.15, 2.53]< 193%3 studies (3/-)75.4 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 0.55 [0.21, 1.42]< 148%3 studies (3/-)89.2 %some concernnot evaluable moderatenon 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) 0.53 [0.21, 1.34]< 169%3 studies (3/-)91.0 %some concernnot evaluable moderatenon important-
Diarrhoea TRAE (grade 3-4) 0.71 [0.27, 1.90]< 177%3 studies (3/-)75.0 %some concernnot evaluable moderatenon 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-
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) 0.85 [0.27, 2.66]< 178%3 studies (3/-)60.8 %some concernnot evaluable moderatenon 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-
Hypothyroidism TRAE (grade 3-4) 1.94 [0.18, 21.47]< 10%2 studies (2/-)29.6 %some concernnot evaluable moderatenon 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-
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) 0.60 [0.21, 1.75]< 176%3 studies (3/-)82.3 %some concernnot evaluable moderatenon important-
Neutropenia TRAE (grade 3-4) 0.66 [0.26, 1.66]< 188%3 studies (3/-)81.1 %some concernnot evaluable moderatenon important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 1.04 [0.32, 3.44]< 160%3 studies (3/-)47.2 %some concernnot evaluable moderatenon important-
Peripheral neuropathy TRAE (grade 3-4) 1.37 [0.82, 2.31]< 10%3 studies (3/-)11.7 %some concernnot evaluable moderatenon important-
Peripheral sensory neuropathy TRAE (grade 3-4) 1.33 [0.50, 3.53]< 110%2 studies (2/-)28.5 %some concernnot evaluable moderatenon 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-
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-
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) 1.00 [0.38, 2.62]< 146%3 studies (3/-)50.3 %some concernnot evaluable moderatenon important-
Vomiting TRAE (grade 3-4) 0.57 [0.23, 1.40]< 157%3 studies (3/-)88.9 %some concernnot evaluable moderatenon 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.