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urothelial cancer (UC) - bladder cancer (BC), durvalumab alone , 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) 0.99 [0.83, 1.18]< 10%1 study (1/-)54.6 %NAnot evaluable crucial-
progression or deaths (PFS) 0.77 [0.54, 1.09]< 10%1 study (1/-)93.0 %NAnot evaluable important-
DOR 0.35 [0.20, 0.62]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
objective responses (ORR) 0.36 [0.26, 0.49]> 10%1 study (1/-)0.0 %NAnot evaluable non important-

safety endpoints 00

AE (grade 3-4) 0.37 [0.27, 0.52]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
AE leading to treatment discontinuation (any grade) 0.66 [0.43, 1.03]< 10%1 study (1/-)96.7 %NAnot evaluable non important-
SAE (any grade) 1.01 [0.74, 1.39]< 10%1 study (1/-)46.3 %NAnot evaluable non important-
STRAE (any grade) 0.50 [0.31, 0.81]< 10%1 study (1/-)99.8 %NAnot evaluable non important-
TRAE (any grade) 0.13 [0.09, 0.21]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
TRAE (grade 3-4) 0.10 [0.07, 0.15]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
TRAE leading to death (grade 5) 1.82 [0.16, 20.16]< 10%1 study (1/-)31.4 %NAnot evaluable non important-
TRAE leading to discontinuation (any grade) 0.46 [0.26, 0.79]< 10%1 study (1/-)99.7 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Abdominal pain TRAE (grade 3-4) 3.64 [0.16, 81.12]< 10%1 study (1/-)21.0 %NAnot evaluable non important-
Acute kidney injury TRAE (grade 3-4) 0.45 [0.02, 13.55]< 10%1 study (1/-)67.4 %NAnot evaluable non important-
Adrenal insufficiency TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 1.82 [0.06, 54.35]< 10%1 study (1/-)36.7 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.05 [0.02, 0.13]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Arthralgia TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Arthritis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.25 [0.05, 1.24]< 10%1 study (1/-)95.5 %NAnot evaluable non important-
Blood creatinine increased TRAE (grade 3-4) 0.45 [0.02, 13.55]< 10%1 study (1/-)67.4 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 0.68 [0.15, 3.05]< 10%1 study (1/-)69.3 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 0.36 [0.07, 1.86]< 10%1 study (1/-)88.8 %NAnot evaluable non important-
Dyspnoea TRAE (grade 3-4) 3.64 [0.16, 81.12]< 10%1 study (1/-)21.0 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.11 [0.01, 0.89]< 10%1 study (1/-)98.0 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 0.15 [0.01, 3.01]< 10%1 study (1/-)89.0 %NAnot evaluable non important-
Gastritis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Guillain-Barré syndrome TRAE (grade 3-4) 1.82 [0.06, 54.35]< 10%1 study (1/-)36.7 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 5.48 [0.27, 109.88]< 10%1 study (1/-)13.6 %NAnot evaluable non important-
Hypersensitivity TRAE (grade 3-4) 0.45 [0.02, 13.55]< 10%1 study (1/-)67.4 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Hypophysitis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 0.91 [0.13, 6.48]< 10%1 study (1/-)53.9 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 2.74 [0.28, 26.45]< 10%1 study (1/-)19.4 %NAnot evaluable non important-
Increased lipase level TRAE (grade 3-4) 6.46 [0.79, 52.82]< 10%1 study (1/-)4.2 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 0.04 [0.00, 0.62]< 10%1 study (1/-)98.8 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 3.64 [0.16, 81.12]< 10%1 study (1/-)21.0 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 1.82 [0.06, 54.35]< 10%1 study (1/-)36.7 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.06 [0.00, 0.97]< 10%1 study (1/-)97.5 %NAnot evaluable non important-
Nephritis TRAE (grade 3-4) 3.64 [0.16, 81.12]< 10%1 study (1/-)21.0 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.01 [0.00, 0.09]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Pancreatitis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Pancytopenia TRAE (grade 3-4) 0.11 [0.01, 2.13]< 10%1 study (1/-)92.5 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 3.64 [0.16, 81.12]< 10%1 study (1/-)21.0 %NAnot evaluable non important-
Pruritic rash TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 1.82 [0.06, 54.35]< 10%1 study (1/-)36.7 %NAnot evaluable non important-
Pyrexia TRAE (grade 3-4) 0.23 [0.01, 5.02]< 10%1 study (1/-)82.3 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 3.64 [0.16, 81.12]< 10%1 study (1/-)21.0 %NAnot evaluable non important-
Sepsis TRAE (grade 3-4) 0.91 [0.06, 14.56]< 10%1 study (1/-)52.7 %NAnot evaluable non important-
Stevens-Johnson syndrome TRAE (grade 3-4) 1.82 [0.06, 54.35]< 10%1 study (1/-)36.7 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 0.02 [0.00, 0.29]< 10%1 study (1/-)99.7 %NAnot evaluable non important-
Thyroiditis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.09 [0.00, 1.64]< 10%1 study (1/-)94.6 %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.