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mUC - L2 - all population, 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) 0.80 [0.70, 0.93]< 121%2 studies (2/-)99.9 %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) 0.96 [0.81, 1.14]< 10%2 studies (2/-)66.7 %some concernnot evaluable moderateimportant-
DOR 0.85 [0.03, 23.54]< 197%2 studies (2/-)53.9 %some concernnot evaluable moderatenon important-
objective responses (ORR) 1.42 [0.69, 2.92]> 182%2 studies (2/-)82.7 %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) 0.34 [0.18, 0.64]< 10%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 0.72 [0.55, 0.94]< 135%2 studies (2/-)99.3 %some concernnot evaluable moderatenon important-
AE leading to death (grade 5) 1.11 [0.65, 1.91]< 10%2 studies (2/-)35.1 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 0.47 [0.28, 0.77]< 151%2 studies (2/-)99.8 %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) 0.92 [0.70, 1.19]< 10%1 study (1/-)74.4 %NAnot evaluable non important-
STRAE (any grade) 0.56 [0.40, 0.78]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
TRAE (any grade) 0.22 [0.14, 0.36]< 160%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.25 [0.14, 0.45]< 179%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 0.60 [0.24, 1.47]< 10%2 studies (2/-)86.9 %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) 1.92 [0.06, 57.51]< 10%1 study (1/-)35.5 %NAnot evaluable non 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) 0.19 [0.04, 1.01]< 176%2 studies (2/-)97.4 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 0.36 [0.16, 0.78]< 10%2 studies (2/-)99.5 %some concernnot evaluable moderatenon important-
Colitis TRAE (grade 3-4) 5.81 [0.29, 116.49]< 10%1 study (1/-)12.8 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 0.04 [0.00, 0.27]< 10%2 studies (2/-)99.9 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 0.16 [0.01, 3.17]< 10%1 study (1/-)88.3 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 1.44 [0.24, 8.71]< 10%1 study (1/-)34.5 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.33 [0.16, 0.67]< 10%2 studies (2/-)99.9 %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-
Hyperthyroidism TRAE (grade 3-4) 0.96 [0.02, 48.49]< 10%1 study (1/-)50.8 %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-
Myositis TRAE (grade 3-4) 0.48 [0.02, 14.32]< 10%1 study (1/-)66.2 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.24 [0.03, 2.13]< 10%1 study (1/-)89.9 %NAnot evaluable non important-
Nephritis TRAE (grade 3-4) 3.86 [0.17, 85.92]< 10%1 study (1/-)20.0 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.03 [0.01, 0.10]< 10%2 studies (2/-)100.0 %some concernnot evaluable moderatenon 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) 9.75 [0.53, 179.40]< 10%1 study (1/-)6.5 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 0.48 [0.02, 14.32]< 10%1 study (1/-)66.2 %NAnot evaluable non important-
Severe skin reaction TRAE (grade 3-4) 0.32 [0.03, 3.07]< 10%1 study (1/-)83.8 %NAnot evaluable non important-
Thyroiditis TRAE (grade 3-4) 0.96 [0.02, 48.49]< 10%1 study (1/-)50.8 %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) 0.65 [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-
Weight decreased AE (grade 3-4) 3.86 [0.17, 85.92]< 10%1 study (1/-)20.0 %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.