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urothelial cancer (UC) - bladder cancer (BC), immune chekpoint inhibitors 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) 0.84 [0.77, 0.92]< 10%4 studies (4/-)100.0 %some concernnot evaluable moderatecrucial-
deaths (OS) (extension) 0.77 [0.66, 0.90]< 138%2 studies (2/-)100.0 %some concernnot evaluable moderateimportant-
PFS (extension) 0.96 [0.79, 1.16]< 10%1 study (1/-)66.1 %NAnot evaluable important-
progression or deaths (PFS) 1.00 [0.78, 1.28]< 182%4 studies (4/-)50.0 %some concernnot evaluable moderateimportant-
CRR 1.96 [1.21, 3.17]> 10%1 study (1/-)99.7 %NAnot evaluable non important-
DOR 0.78 [0.17, 3.72]< 193%3 studies (3/-)62.0 %some concernnot evaluable moderatenon important-
objective responses (ORR) 1.04 [0.63, 1.72]> 188%4 studies (4/-)56.5 %some concernnot evaluable moderatenon important-
objective responses (ORR) (extension) 2.16 [1.34, 3.48]> 10%1 study (1/-)99.9 %NAnot evaluable non important-

safety endpoints 00

AE (any grade) 0.50 [0.19, 1.33]< 157%3 studies (3/-)91.8 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 0.77 [0.62, 0.95]< 124%3 studies (3/-)99.3 %some concernnot evaluable moderatenon important-
AE (grade 3-5) 0.38 [0.26, 0.54]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
AE leading to death (grade 5) 1.54 [0.89, 2.68]< 157%4 studies (4/-)6.2 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 0.69 [0.43, 1.11]< 182%4 studies (4/-)93.6 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (grade 3-4) 0.85 [0.44, 1.65]< 10%1 study (1/-)68.1 %NAnot evaluable non important-
SAE (any grade) 1.01 [0.83, 1.22]< 13%2 studies (2/-)47.1 %some concernnot evaluable moderatenon important-
STRAE (any grade) 0.67 [0.33, 1.39]< 192%3 studies (3/-)85.9 %some concernnot evaluable moderatenon important-
TRAE (any grade) 0.24 [0.10, 0.58]< 191%4 studies (4/-)99.9 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.27 [0.10, 0.74]< 197%4 studies (4/-)99.4 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 0.95 [0.47, 1.92]< 17%4 studies (4/-)56.0 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.32 [0.15, 0.70]< 170%2 studies (2/-)99.8 %some concernnot evaluable moderatenon important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 1.53 [0.12, 19.99]< 10%2 studies (2/-)37.4 %some concernnot evaluable moderatenon important-
Alopecia TRAE (grade 3-4) 0.24 [0.01, 5.31]< 10%1 study (1/-)81.5 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.17 [0.03, 0.96]< 193%4 studies (4/-)97.7 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 0.44 [0.12, 1.58]< 174%4 studies (4/-)89.5 %some concernnot evaluable moderatenon important-
Colitis TRAE (grade 3-4) 4.97 [0.85, 29.26]< 10%2 studies (2/-)3.9 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.14 [0.01, 1.71]< 167%3 studies (3/-)93.7 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 0.63 [0.13, 3.13]< 120%3 studies (3/-)71.1 %some concernnot evaluable moderatenon important-
Diabetes TRAE (grade 3-4) 2.27 [0.08, 67.88]< 10%1 study (1/-)32.1 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 1.07 [0.37, 3.10]< 10%2 studies (2/-)45.3 %some concernnot evaluable moderatenon important-
Fatigue TRAE (grade 3-4) 0.56 [0.22, 1.41]< 161%4 studies (4/-)88.9 %some concernnot evaluable moderatenon important-
Febrile neutropenia TRAE (grade 3-4) 0.04 [0.00, 0.27]< 10%1 study (1/-)99.9 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 2.27 [0.08, 67.88]< 10%1 study (1/-)32.1 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 1.04 [0.07, 16.70]< 10%2 studies (2/-)48.9 %some concernnot evaluable moderatenon important-
Hypophysitis TRAE (grade 3-4) 2.27 [0.08, 67.88]< 10%1 study (1/-)32.1 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 2.27 [0.08, 67.88]< 10%1 study (1/-)32.1 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 0.96 [0.02, 48.49]< 10%1 study (1/-)50.8 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 0.01 [0.00, 0.13]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 1.13 [0.02, 57.26]< 10%1 study (1/-)47.6 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 0.69 [0.05, 9.04]< 10%2 studies (2/-)61.0 %some concernnot evaluable moderatenon important-
Nausea TRAE (grade 3-4) 0.51 [0.14, 1.82]< 134%3 studies (3/-)84.9 %some concernnot evaluable moderatenon important-
Nephritis TRAE (grade 3-4) 3.03 [0.31, 29.97]< 10%2 studies (2/-)17.3 %some concernnot evaluable moderatenon important-
Neutropenia TRAE (grade 3-4) 0.05 [0.00, 1.28]< 194%4 studies (4/-)96.3 %some concernnot evaluable moderatenon important-
Pancreatitis TRAE (grade 3-4) 4.55 [0.20, 101.37]< 10%1 study (1/-)17.2 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 0.15 [0.03, 0.83]< 10%2 studies (2/-)98.5 %some concernnot evaluable moderatenon important-
Pneumonitis TRAE (grade 3-4) 6.02 [1.04, 34.78]< 10%2 studies (2/-)2.3 %some concernnot evaluable moderatenon important-
Pruritus TRAE (grade 3-4) 0.96 [0.12, 7.49]< 10%3 studies (3/-)51.4 %some concernnot evaluable moderatenon important-
Rash TRAE (grade 3-4) 0.68 [0.05, 8.83]< 10%2 studies (2/-)61.6 %some concernnot evaluable moderatenon important-
Sarcoidosis TRAE (grade 3-4) 1.13 [0.02, 57.26]< 10%1 study (1/-)47.6 %NAnot evaluable non important-
Severe skin reaction TRAE (grade 3-4) 0.66 [0.15, 2.90]< 10%2 studies (2/-)71.0 %some concernnot evaluable moderatenon important-
Thrombocytopenia TRAE (grade 3-4) 0.16 [0.00, 8.79]< 193%2 studies (2/-)81.0 %some concernnot evaluable moderatenon important-
Thyroiditis TRAE (grade 3-4) 1.57 [0.12, 20.47]< 10%2 studies (2/-)36.7 %some concernnot evaluable moderatenon important-
Vomiting TRAE (grade 3-4) 0.14 [0.02, 1.12]< 10%1 study (1/-)96.8 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Abdominal pain AE (grade 3-4) 0.40 [0.10, 1.58]< 10%1 study (1/-)90.3 %NAnot evaluable non important-
Acute kidney injury AE (grade 3-4) 2.27 [0.58, 8.88]< 10%1 study (1/-)12.0 %NAnot evaluable non important-
Alopecia AE (grade 3-4) 0.16 [0.01, 3.17]< 10%1 study (1/-)88.3 %NAnot evaluable non important-
Anaemia AE (grade 3-4) 0.89 [0.56, 1.44]< 158%2 studies (2/-)67.6 %some concernnot evaluable moderatenon important-
Arthralgia AE (grade 3-4) 0.16 [0.01, 3.17]< 10%1 study (1/-)88.3 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 0.50 [0.05, 4.78]< 188%2 studies (2/-)72.5 %some concernnot evaluable moderatenon important-
Back pain AE (grade 3-4) 1.92 [0.17, 21.35]< 10%1 study (1/-)29.8 %NAnot evaluable non important-
Blood and lymphatic system disorders AE (grade 3-4) 0.24 [0.15, 0.40]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Blood creatinine increased AE (grade 3-4) 1.92 [0.17, 21.35]< 10%1 study (1/-)29.8 %NAnot evaluable non important-
Cardiac disorders AE (grade 3-4) 0.72 [0.16, 3.23]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Constipation AE (grade 3-4) 0.35 [0.09, 1.34]< 10%1 study (1/-)93.6 %NAnot evaluable non important-
Cough AE (grade 3-4) 1.92 [0.06, 57.51]< 10%1 study (1/-)35.5 %NAnot evaluable non important-
Decreased appetite AE (grade 3-4) 3.28 [0.89, 12.06]< 10%1 study (1/-)3.7 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 0.96 [0.24, 3.87]< 10%1 study (1/-)52.4 %NAnot evaluable non important-
Dizziness AE (grade 3-4) 0.48 [0.02, 14.32]< 10%1 study (1/-)66.2 %NAnot evaluable non important-
Dry skin AE (grade 3-4) 0.96 [0.02, 48.49]< 10%1 study (1/-)50.8 %NAnot evaluable non important-
Dysgeusia AE (grade 3-4) 0.96 [0.02, 48.49]< 10%1 study (1/-)50.8 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 1.61 [0.38, 6.80]< 10%1 study (1/-)25.9 %NAnot evaluable non important-
Endocrine disorders AE (grade 3-4) 5.81 [0.29, 116.49]< 10%1 study (1/-)12.8 %NAnot evaluable non important-
Eye disorders AE (grade 3-4) 3.86 [0.17, 85.92]< 10%1 study (1/-)20.0 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.65 [0.40, 1.04]< 10%2 studies (2/-)96.4 %some concernnot evaluable moderatenon important-
Febrile neutropenia AE (grade 3-4) 0.25 [0.00, 17.01]< 188%2 studies (2/-)73.4 %some concernnot evaluable moderatenon important-
Gastrointestinal disorders AE (grade 3-4) 0.42 [0.24, 0.75]< 10%1 study (1/-)99.9 %NAnot evaluable non important-
General disorders and administration site conditions AE (grade 3-4) 0.49 [0.28, 0.86]< 10%1 study (1/-)99.4 %NAnot evaluable non important-
Headache AE (grade 3-4) 1.92 [0.06, 57.51]< 10%1 study (1/-)35.5 %NAnot evaluable non important-
Hypertension AE (grade 3-4) 2.22 [1.05, 4.68]< 10%1 study (1/-)1.8 %NAnot evaluable non important-
Hypothyroidism AE (grade 3-4) 0.96 [0.02, 48.49]< 10%1 study (1/-)50.8 %NAnot evaluable non important-
Increase AST AE (grade 3-4) 11.75 [0.65, 211.40]< 10%1 study (1/-)4.9 %NAnot evaluable non important-
Increased ALT AE (grade 3-4) 5.81 [0.29, 116.49]< 10%1 study (1/-)12.8 %NAnot evaluable non important-
Infections and infestations AE (grade 3-4) 1.22 [0.72, 2.06]< 10%1 study (1/-)22.8 %NAnot evaluable non important-
Injury, poisoning and procedure AE (grade 3-4) 1.45 [0.40, 5.19]< 10%1 study (1/-)28.5 %NAnot evaluable non important-
Investigations AE (grade 3-4) 0.46 [0.26, 0.79]< 10%1 study (1/-)99.7 %NAnot evaluable non important-
Leucopenia AE (grade 3-4) 0.74 [0.44, 1.24]< 10%1 study (1/-)87.3 %NAnot evaluable non important-
Metabolism and nutrition disorders AE (grade 3-4) 1.07 [0.62, 1.84]< 10%1 study (1/-)40.4 %NAnot evaluable non important-
Mucosal inflammation AE (grade 3-4) 0.24 [0.03, 2.13]< 10%1 study (1/-)89.9 %NAnot evaluable non important-
Musculoskeletal and connective tissue disorders AE (grade 3-4) 1.36 [0.59, 3.12]< 10%1 study (1/-)23.4 %NAnot evaluable non important-
Myalgia AE (grade 3-4) 1.92 [0.06, 57.51]< 10%1 study (1/-)35.5 %NAnot evaluable non important-
Nausea AE (grade 3-4) 0.58 [0.28, 1.22]< 10%2 studies (2/-)92.5 %some concernnot evaluable moderatenon important-
Nervous system disorders AE (grade 3-4) 0.27 [0.10, 0.74]< 10%1 study (1/-)99.5 %NAnot evaluable non important-
Neutropenia AE (grade 3-4) 0.15 [0.00, 16.84]< 191%2 studies (2/-)77.7 %some concernnot evaluable moderatenon important-
Peripheral neuropathy AE (grade 3-4) 0.24 [0.01, 5.31]< 10%1 study (1/-)81.5 %NAnot evaluable non important-
Peripheral oedema AE (grade 3-4) 0.24 [0.01, 5.31]< 10%1 study (1/-)81.5 %NAnot evaluable non important-
Pruritus AE (grade 3-4) 0.48 [0.02, 14.32]< 10%1 study (1/-)66.2 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 0.64 [0.11, 3.84]< 10%1 study (1/-)68.8 %NAnot evaluable non important-
Rash AE (grade 3-4) 1.92 [0.06, 57.51]< 10%1 study (1/-)35.5 %NAnot evaluable non important-
Renal and urinary disorders AE (grade 3-4) 2.77 [1.31, 5.84]< 10%1 study (1/-)0.4 %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.