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urothelial cancer (UC) - bladder cancer (BC), anti-PD-(L)1 , 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 [0.80, 0.93]< 135%9 studies (9/-)100.0 %some concernnot evaluable moderatecrucial-
deaths (OS) (extension) 0.77 [0.70, 0.85]< 10%3 studies (3/-)100.0 %some concernnot evaluable moderateimportant-
PFS (extension) 0.72 [0.41, 1.26]< 195%2 studies (2/-)87.4 %some concernnot evaluable moderateimportant-
progression or deaths (PFS) 0.87 [0.71, 1.06]< 184%7 studies (7/-)91.8 %some concernnot evaluable moderateimportant-
RFS/DFS 0.72 [0.59, 0.88]< 10%1 study (1/-)99.9 %NAnot evaluable important-
CRR 1.96 [1.21, 3.17]> 10%1 study (1/-)99.7 %NAnot evaluable non important-
DCR 1.85 [1.35, 2.54]> 10%1 study (1/-)100.0 %NAnot evaluable non important-
DMFS 0.75 [0.59, 0.95]< 10%1 study (1/-)99.2 %NAnot evaluable non important-
DOR 0.50 [0.20, 1.24]< 191%5 studies (5/-)93.3 %some concernnot evaluable moderatenon important-
events or deaths (EFS) 0.80 [0.63, 1.01]< 157%2 studies (2/-)96.9 %some concernnot evaluable moderatenon important-
objective responses (ORR) 0.99 [0.60, 1.62]> 194%8 studies (8/-)47.8 %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) 0.85 [0.13, 5.43]< 194%5 studies (5/-)56.7 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 0.65 [0.27, 1.56]< 198%6 studies (6/-)83.1 %some concernnot evaluable moderatenon 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) 1.80 [1.18, 2.75]< 150%7 studies (7/-)0.3 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 0.76 [0.40, 1.45]< 194%8 studies (8/-)79.6 %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) 1.03 [0.84, 1.27]< 158%5 studies (5/-)38.3 %some concernnot evaluable moderatenon important-
STRAE (any grade) 0.73 [0.45, 1.18]< 189%7 studies (7/-)89.9 %some concernnot evaluable moderatenon important-
TRAE (any grade) 0.61 [0.16, 2.31]< 198%8 studies (8/-)76.4 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.39 [0.16, 0.97]< 198%9 studies (9/-)97.9 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 0.71 [0.36, 1.42]< 142%8 studies (8/-)83.2 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.57 [0.22, 1.47]< 184%4 studies (4/-)87.8 %some concernnot evaluable moderatenon 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) 1.48 [0.15, 14.66]< 10%2 studies (2/-)36.9 %lownot evaluable highnon important-
Adrenal insufficiency TRAE (grade 3-4) 1.31 [0.29, 5.98]< 10%6 studies (6/-)36.5 %some concernserious moderatenon important-
Alopecia TRAE (grade 3-4) 0.60 [0.06, 5.94]< 10%2 studies (2/-)66.8 %some concernnot evaluable moderatenon important-
Anaemia TRAE (grade 3-4) 0.17 [0.06, 0.49]< 193%7 studies (7/-)99.9 %some concernserious moderatenon important-
Arthralgia TRAE (grade 3-4) 1.43 [0.11, 18.64]< 10%2 studies (2/-)39.4 %some concernnot evaluable moderatenon important-
Arthritis TRAE (grade 3-4) 0.95 [0.06, 15.28]< 10%2 studies (2/-)51.3 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 0.61 [0.31, 1.17]< 147%9 studies (9/-)93.1 %some concernnot evaluable moderatenon important-
Blood creatinine increased TRAE (grade 3-4) 0.95 [0.09, 10.48]< 10%2 studies (2/-)51.7 %lownot evaluable highnon important-
Chills TRAE (grade 3-4) 1.00 [0.02, 50.69]< 10%1 study (1/-)49.9 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 2.50 [0.91, 6.91]< 10%6 studies (6/-)3.8 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.21 [0.04, 1.05]< 138%5 studies (5/-)97.1 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 0.80 [0.34, 1.85]< 10%7 studies (7/-)70.1 %some concernnot evaluable moderatenon important-
Dermatitis acneiform TRAE (grade 3-4) 0.99 [0.02, 50.11]< 10%1 study (1/-)50.2 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 1.40 [0.27, 7.25]< 10%5 studies (5/-)34.7 %some concernserious moderatenon important-
Diarrhoea TRAE (grade 3-4) 1.06 [0.54, 2.06]< 10%6 studies (6/-)43.2 %some concernnot evaluable moderatenon important-
Dry skin TRAE (grade 3-4) 1.00 [0.02, 50.69]< 10%1 study (1/-)49.9 %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-
Eczema TRAE (grade 3-4) 0.99 [0.02, 50.11]< 10%1 study (1/-)50.2 %NAnot evaluable non important-
Endocrine disorders TRAE (grade 3-4) 1.99 [0.07, 59.38]< 10%1 study (1/-)34.8 %NAnot evaluable non important-
Erythema TRAE (grade 3-4) 0.99 [0.02, 50.11]< 10%1 study (1/-)50.2 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.59 [0.33, 1.07]< 133%9 studies (9/-)95.8 %some concernnot evaluable moderatenon important-
Febrile neutropenia TRAE (grade 3-4) 0.06 [0.01, 0.30]< 10%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
Gastritis TRAE (grade 3-4) 0.91 [0.02, 45.86]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Gastrointestinal disorders TRAE (grade 3-4) 2.00 [0.50, 8.06]< 10%1 study (1/-)16.5 %NAnot evaluable non important-
Guillain-Barré syndrome TRAE (grade 3-4) 1.91 [0.17, 21.12]< 10%2 studies (2/-)30.0 %some concernnot evaluable moderatenon important-
Hepatitis TRAE (grade 3-4) 3.07 [0.47, 19.99]< 10%3 studies (3/-)12.2 %some concernnot evaluable moderatenon 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) 1.18 [0.22, 6.46]< 10%5 studies (5/-)42.4 %some concernserious moderatenon important-
Hypophysitis TRAE (grade 3-4) 2.72 [0.39, 19.09]< 10%3 studies (3/-)15.9 %some concernnot evaluable moderatenon important-
Hypothyroidism TRAE (grade 3-4) 2.19 [0.40, 12.08]< 10%4 studies (4/-)18.6 %some concernnot evaluable moderatenon important-
Increase AST TRAE (grade 3-4) 1.10 [0.20, 6.05]< 10%2 studies (2/-)45.5 %some concernnot evaluable moderatenon important-
Increased ALT TRAE (grade 3-4) 3.12 [0.50, 19.47]< 10%2 studies (2/-)11.3 %some concernnot evaluable moderatenon important-
Increased lipase level TRAE (grade 3-4) 9.73 [1.80, 52.75]< 10%2 studies (2/-)0.4 %some concernnot evaluable moderatenon important-
Infusion-related reactions TRAE (grade 3-4) 2.21 [0.29, 16.94]< 10%3 studies (3/-)22.4 %some concernnot evaluable moderatenon important-
Leucopenia TRAE (grade 3-4) 0.07 [0.00, 1.54]< 184%3 studies (3/-)95.2 %some concernnot evaluable moderatenon important-
Maculopapular rash TRAE (grade 3-4) 3.98 [0.18, 88.64]< 10%1 study (1/-)19.4 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 2.19 [0.30, 15.87]< 10%3 studies (3/-)21.9 %some concernnot evaluable moderatenon important-
Myositis TRAE (grade 3-4) 1.41 [0.29, 6.75]< 10%5 studies (5/-)33.5 %some concernnot evaluable moderatenon important-
Nausea TRAE (grade 3-4) 0.59 [0.30, 1.14]< 10%8 studies (8/-)94.2 %some concernnot evaluable moderatenon important-
Nephritis TRAE (grade 3-4) 2.39 [0.61, 9.40]< 10%6 studies (6/-)10.7 %some concernserious moderatenon important-
Neutropenia TRAE (grade 3-4) 0.08 [0.02, 0.34]< 191%7 studies (7/-)100.0 %some concernserious moderatenon important-
Pancreatitis TRAE (grade 3-4) 2.68 [0.50, 14.20]< 10%4 studies (4/-)12.4 %some concernnot evaluable moderatenon important-
Pancytopenia TRAE (grade 3-4) 0.11 [0.01, 2.13]< 10%1 study (1/-)92.5 %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) 3.73 [1.22, 11.44]< 10%6 studies (6/-)1.1 %some concernnot evaluable moderatenon important-
Pruritic rash TRAE (grade 3-4) 0.95 [0.06, 15.19]< 10%2 studies (2/-)51.5 %lownot evaluable highnon important-
Pruritus TRAE (grade 3-4) 1.60 [0.46, 5.52]< 10%8 studies (8/-)22.8 %some concernserious moderatenon important-
Pyrexia TRAE (grade 3-4) 0.40 [0.04, 4.57]< 10%2 studies (2/-)76.8 %some concernnot evaluable moderatenon important-
Rash TRAE (grade 3-4) 2.58 [0.82, 8.15]< 10%7 studies (7/-)5.3 %some concernnot evaluable moderatenon important-
Renal and urinary disorders TRAE (grade 3-4) 8.01 [0.42, 152.12]< 10%1 study (1/-)8.5 %NAnot evaluable non important-
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) 5.99 [0.30, 120.06]< 10%1 study (1/-)12.4 %NAnot evaluable non important-
Sarcoidosis TRAE (grade 3-4) 1.05 [0.07, 16.88]< 10%2 studies (2/-)48.5 %some concernnot evaluable moderatenon important-
Sepsis TRAE (grade 3-4) 0.91 [0.06, 14.56]< 10%1 study (1/-)52.7 %NAnot evaluable non 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-
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) 0.20 [0.05, 0.71]< 185%5 studies (5/-)99.4 %some concernserious moderatenon important-
Thyroiditis TRAE (grade 3-4) 1.16 [0.24, 5.50]< 10%6 studies (6/-)42.7 %some concernserious moderatenon important-
Urticaria TRAE (grade 3-4) 0.99 [0.02, 50.11]< 10%1 study (1/-)50.2 %NAnot evaluable non important-
Uveitis TRAE (grade 3-4) 1.00 [0.02, 50.69]< 10%1 study (1/-)49.9 %NAnot evaluable non important-
Vitiligo TRAE (grade 3-4) 1.00 [0.02, 50.69]< 10%1 study (1/-)49.9 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.34 [0.06, 1.92]< 160%3 studies (3/-)88.9 %some concernnot evaluable moderatenon important-

AE (grade 3-4) endpoints 00

hepatitis (Autoimmune) AE (grade 3-4) 2.01 [0.07, 60.08]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
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) 0.51 [0.14, 1.84]< 196%4 studies (4/-)84.7 %some concernnot evaluable moderatenon important-
Arthralgia AE (grade 3-4) 0.78 [0.03, 18.57]< 154%2 studies (2/-)56.1 %some concernnot evaluable moderatenon important-
Asthenia AE (grade 3-4) 0.48 [0.16, 1.41]< 175%4 studies (4/-)90.9 %some concernnot evaluable moderatenon important-
Back pain AE (grade 3-4) 0.65 [0.22, 1.92]< 10%2 studies (2/-)78.1 %some concernnot evaluable moderatenon 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-

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.