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urothelial cancer (UC) - bladder cancer (BC), 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) 0.84 [0.74, 0.96]< 124%3 studies (3/-)99.6 %some concernnot evaluable moderatecrucial-
deaths (OS) (extension) 0.70 [0.57, 0.85]< 10%1 study (1/-)100.0 %NAnot evaluable important-
PFS (extension) 0.96 [0.79, 1.16]< 10%1 study (1/-)66.1 %NAnot evaluable important-
progression or deaths (PFS) 1.01 [0.74, 1.39]< 189%3 studies (3/-)47.6 %some concernnot evaluable moderateimportant-
DOR 4.66 [1.83, 11.87]< 10%1 study (1/-)0.1 %NAnot evaluable non important-
objective responses (ORR) 1.17 [0.53, 2.59]> 193%3 studies (3/-)64.8 %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) 0.28 [0.10, 0.75]< 10%1 study (1/-)99.4 %NAnot evaluable non important-
AE (grade 3-4) 0.61 [0.43, 0.86]< 10%1 study (1/-)99.7 %NAnot evaluable non important-
AE (grade 3-5) 0.76 [0.19, 3.00]< 196%2 studies (2/-)65.4 %some concernnot evaluable moderatenon important-
AE leading to death (grade 5) 2.88 [1.73, 4.78]< 116%3 studies (3/-)0.0 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 1.05 [0.52, 2.14]< 187%3 studies (3/-)44.5 %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-
STRAE (any grade) 0.68 [0.23, 1.96]< 194%2 studies (2/-)76.3 %some concernnot evaluable moderatenon important-
TRAE (any grade) 0.12 [0.05, 0.25]< 175%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.26 [0.05, 1.37]< 198%3 studies (3/-)94.3 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 1.00 [0.38, 2.69]< 10%3 studies (3/-)49.6 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.48 [0.25, 0.93]< 10%1 study (1/-)98.5 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 1.68 [0.22, 13.01]< 10%3 studies (3/-)31.2 %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) 0.11 [0.01, 1.60]< 196%3 studies (3/-)94.5 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 0.32 [0.07, 1.52]< 162%3 studies (3/-)92.3 %some concernnot evaluable moderatenon important-
Colitis TRAE (grade 3-4) 3.59 [0.86, 14.94]< 10%3 studies (3/-)4.0 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.33 [0.05, 1.99]< 131%3 studies (3/-)88.6 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 0.29 [0.07, 1.20]< 10%3 studies (3/-)95.5 %some concernnot evaluable moderatenon important-
Diabetes TRAE (grade 3-4) 2.11 [0.19, 23.33]< 10%2 studies (2/-)27.3 %some concernnot evaluable moderatenon important-
Diarrhoea TRAE (grade 3-4) 1.20 [0.55, 2.63]< 10%3 studies (3/-)32.4 %some concernnot evaluable moderatenon important-
Fatigue TRAE (grade 3-4) 0.53 [0.26, 1.06]< 112%3 studies (3/-)96.3 %some concernnot evaluable moderatenon important-
Hepatitis TRAE (grade 3-4) 2.11 [0.19, 23.33]< 10%2 studies (2/-)27.3 %some concernnot evaluable moderatenon important-
Hyperthyroidism TRAE (grade 3-4) 1.34 [0.16, 11.51]< 10%3 studies (3/-)39.5 %some concernnot evaluable moderatenon important-
Hypophysitis TRAE (grade 3-4) 3.89 [0.41, 36.85]< 10%2 studies (2/-)12.0 %some concernnot evaluable moderatenon important-
Hypothyroidism TRAE (grade 3-4) 3.06 [0.31, 30.30]< 10%2 studies (2/-)17.1 %some concernnot evaluable moderatenon 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) 0.09 [0.00, 7.03]< 189%2 studies (2/-)85.4 %some concernnot evaluable moderatenon important-
Myocarditis TRAE (grade 3-4) 1.55 [0.12, 20.23]< 10%2 studies (2/-)37.0 %some concernnot evaluable moderatenon important-
Myositis TRAE (grade 3-4) 0.77 [0.09, 6.59]< 10%3 studies (3/-)59.4 %some concernnot evaluable moderatenon important-
Nausea TRAE (grade 3-4) 0.54 [0.24, 1.19]< 10%3 studies (3/-)93.6 %some concernnot evaluable moderatenon important-
Nephritis TRAE (grade 3-4) 2.65 [0.40, 17.69]< 10%3 studies (3/-)15.9 %some concernnot evaluable moderatenon important-
Neutropenia TRAE (grade 3-4) 0.04 [0.00, 2.29]< 191%3 studies (3/-)93.6 %some concernnot evaluable moderatenon important-
Pancreatitis TRAE (grade 3-4) 4.23 [0.47, 37.98]< 10%2 studies (2/-)10.0 %some concernnot evaluable moderatenon important-
Peripheral neuropathy TRAE (grade 3-4) 0.24 [0.01, 5.31]< 10%1 study (1/-)81.5 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 4.61 [1.15, 18.48]< 10%3 studies (3/-)1.6 %some concernnot evaluable moderatenon important-
Pruritus TRAE (grade 3-4) 1.72 [0.24, 12.08]< 10%3 studies (3/-)29.4 %some concernnot evaluable moderatenon important-
Rash TRAE (grade 3-4) 2.23 [0.35, 14.10]< 10%2 studies (2/-)19.8 %some concernnot evaluable moderatenon important-
Sarcoidosis TRAE (grade 3-4) 1.05 [0.07, 16.88]< 10%2 studies (2/-)48.5 %some concernnot evaluable moderatenon important-
Severe skin reaction TRAE (grade 3-4) 1.36 [0.32, 5.68]< 141%3 studies (3/-)33.8 %some concernnot evaluable moderatenon important-
Thrombocytopenia TRAE (grade 3-4) 0.14 [0.00, 5.55]< 192%2 studies (2/-)84.9 %some concernnot evaluable moderatenon important-
Thyroiditis TRAE (grade 3-4) 1.36 [0.16, 11.68]< 10%3 studies (3/-)39.0 %some concernnot evaluable moderatenon important-
Vomiting TRAE (grade 3-4) 0.49 [0.07, 3.55]< 168%2 studies (2/-)76.1 %some concernnot evaluable moderatenon 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) 0.65 [0.37, 1.16]< 10%1 study (1/-)92.8 %NAnot evaluable non 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) 0.14 [0.03, 0.63]< 10%1 study (1/-)99.5 %NAnot evaluable non 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) 0.63 [0.28, 1.42]< 10%1 study (1/-)86.9 %NAnot evaluable non important-
Febrile neutropenia AE (grade 3-4) 0.02 [0.00, 0.39]< 10%1 study (1/-)99.5 %NAnot evaluable non 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-
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-
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) 0.72 [0.16, 3.23]< 10%1 study (1/-)66.8 %NAnot evaluable non 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) 0.01 [0.00, 0.18]< 10%1 study (1/-)99.9 %NAnot evaluable non 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-
Respiratory, thoracic and mediastinal disorders AE (grade 3-4) 1.63 [0.70, 3.80]< 10%1 study (1/-)12.8 %NAnot evaluable non important-
Skin and subcutaneous tissue disorders AE (grade 3-4) 0.16 [0.02, 1.31]< 10%1 study (1/-)95.6 %NAnot evaluable non important-
Stomatitis AE (grade 3-4) 0.96 [0.06, 15.41]< 10%1 study (1/-)51.2 %NAnot evaluable non important-
Vascular disorders AE (grade 3-4) 2.71 [0.85, 8.61]< 10%1 study (1/-)4.6 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 0.96 [0.06, 15.41]< 10%1 study (1/-)51.2 %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.