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mML - NA - all population, nivolumab 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) 0.87 [0.66, 1.14]< 10%1 study (1/-)84.1 %NAnot evaluable crucial-
MFS 0.73 [0.56, 0.96]< 10%1 study (1/-)98.8 %NAnot evaluable important-
RFS (extension) 0.71 [0.59, 0.85]< 10%1 study (1/-)100.0 %NAnot evaluable important-
RFS/DFS 0.92 [0.45, 1.89]< 186%3 studies (3/-)59.3 %lownot evaluable highimportant-

safety endpoints 00

AE (any grade) 0.49 [0.20, 1.23]< 10%1 study (1/-)93.6 %NAnot evaluable non important-
AE (grade 3-4) 0.28 [0.21, 0.37]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
AE leading to death (grade 5) 0.95 [0.06, 15.45]< 10%2 studies (2/-)51.3 %lownot evaluable highnon important-
AE leading to treatment discontinuation (any grade) 0.29 [0.07, 1.26]< 187%3 studies (3/-)95.0 %lownot evaluable highnon important-
AE leading to treatment discontinuation (grade 3-4) 0.24 [0.05, 1.09]< 183%3 studies (3/-)96.8 %lownot evaluable highnon important-
SAE (any grade) 0.58 [0.13, 2.64]< 186%2 studies (2/-)75.7 %lownot evaluable highnon important-
SAE (grade 3-4) 0.83 [0.10, 6.97]< 191%2 studies (2/-)56.7 %lownot evaluable highnon important-
STRAE (any grade) 0.97 [0.03, 31.56]< 193%2 studies (2/-)50.6 %lownot evaluable highnon important-
STRAE (grade 3-4) 1.64 [0.02, 132.78]< 188%2 studies (2/-)41.5 %lownot evaluable highnon important-
TRAE (any grade) 0.62 [0.08, 4.75]< 193%3 studies (3/-)67.8 %lownot evaluable highnon important-
TRAE (grade 3-4) 0.49 [0.10, 2.37]< 192%3 studies (3/-)81.1 %lownot evaluable highnon important-
TRAE leading to death (grade 5) 0.52 [0.07, 4.17]< 10%3 studies (3/-)72.8 %lownot evaluable highnon important-
TRAE leading to discontinuation (any grade) 0.28 [0.06, 1.28]< 186%3 studies (3/-)94.9 %lownot evaluable highnon important-
TRAE leading to discontinuation (grade 3-4) 0.19 [0.04, 0.88]< 180%3 studies (3/-)98.3 %lownot evaluable highnon important-

TRAE (grade 3-4) endpoints 00

Abdominal pain TRAE (grade 3-4) 0.73 [0.08, 6.31]< 10%3 studies (3/-)61.1 %lownot evaluable highnon important-
Acute kidney injury TRAE (grade 3-4) 0.64 [0.05, 8.40]< 10%2 studies (2/-)63.3 %lownot evaluable highnon important-
Adrenal insufficiency TRAE (grade 3-4) 0.54 [0.13, 2.22]< 10%3 studies (3/-)80.4 %lownot evaluable highnon important-
Alopecia TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Anaemia TRAE (grade 3-4) 0.64 [0.05, 8.40]< 10%2 studies (2/-)63.3 %lownot evaluable highnon important-
Arthralgia TRAE (grade 3-4) 1.52 [0.30, 7.73]< 10%3 studies (3/-)30.7 %lownot evaluable highnon important-
Asthenia TRAE (grade 3-4) 0.25 [0.03, 2.24]< 10%1 study (1/-)89.1 %NAnot evaluable non important-
Blood and lymphatic system disorders TRAE (grade 3-4) 2.98 [0.27, 32.69]< 10%2 studies (2/-)18.8 %lownot evaluable highnon important-
Blood creatinine increased TRAE (grade 3-4) 0.91 [0.02, 46.72]< 10%1 study (1/-)51.8 %NAnot evaluable non important-
Chills TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Colitis TRAE (grade 3-4) 0.30 [0.03, 3.29]< 10%2 studies (2/-)83.6 %lownot evaluable highnon important-
Cough TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Decreased appetite TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Diabetes TRAE (grade 3-4) 1.94 [0.27, 13.89]< 10%3 studies (3/-)25.6 %lownot evaluable highnon important-
Diarrhoea TRAE (grade 3-4) 0.35 [0.07, 1.69]< 140%3 studies (3/-)90.4 %lownot evaluable highnon important-
Dizziness TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Dry skin TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Dysgeusia TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Dyspepsia TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Dyspnoea TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Endocrine disorders TRAE (grade 3-4) 0.39 [0.05, 3.31]< 120%2 studies (2/-)80.4 %lownot evaluable highnon important-
Eye disorders TRAE (grade 3-4) 0.64 [0.05, 8.40]< 10%2 studies (2/-)63.3 %lownot evaluable highnon important-
Fatigue TRAE (grade 3-4) 0.59 [0.14, 2.54]< 10%3 studies (3/-)75.9 %lownot evaluable highnon important-
Gastritis TRAE (grade 3-4) 0.40 [0.03, 4.62]< 10%2 studies (2/-)76.7 %lownot evaluable highnon important-
Gastrointestinal disorders TRAE (grade 3-4) 0.13 [0.04, 0.40]< 125%3 studies (3/-)100.0 %lownot evaluable highnon important-
General disorders and administration site conditions TRAE (grade 3-4) 0.40 [0.03, 4.62]< 10%2 studies (2/-)76.7 %lownot evaluable highnon important-
Headache TRAE (grade 3-4) 0.28 [0.05, 1.50]< 10%3 studies (3/-)93.0 %lownot evaluable highnon important-
Hepatitis TRAE (grade 3-4) 0.74 [0.07, 7.82]< 149%2 studies (2/-)59.9 %lownot evaluable highnon important-
Hepatobiliary disorders TRAE (grade 3-4) 0.22 [0.06, 0.77]< 150%3 studies (3/-)99.1 %lownot evaluable highnon important-
Hypersensitivity TRAE (grade 3-4) 2.01 [0.07, 59.97]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Hypertension TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Hyperthyroidism TRAE (grade 3-4) 0.50 [0.08, 3.08]< 10%3 studies (3/-)77.1 %lownot evaluable highnon important-
Hypophysitis TRAE (grade 3-4) 0.46 [0.09, 2.47]< 125%3 studies (3/-)81.6 %lownot evaluable highnon important-
Hypothyroidism TRAE (grade 3-4) 0.66 [0.11, 4.05]< 10%3 studies (3/-)67.4 %lownot evaluable highnon important-
Increase AST TRAE (grade 3-4) 0.38 [0.06, 2.20]< 165%3 studies (3/-)85.9 %lownot evaluable highnon important-
Increased ALT TRAE (grade 3-4) 0.31 [0.08, 1.18]< 157%3 studies (3/-)95.7 %lownot evaluable highnon important-
Increased lipase level TRAE (grade 3-4) 0.50 [0.17, 1.45]< 10%2 studies (2/-)89.8 %lownot evaluable highnon important-
Infusion-related reactions TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Leucopenia TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Maculopapular rash TRAE (grade 3-4) 0.21 [0.03, 1.43]< 10%3 studies (3/-)94.4 %lownot evaluable highnon important-
Metabolism and nutrition disorders TRAE (grade 3-4) 1.26 [0.14, 10.99]< 10%2 studies (2/-)41.7 %lownot evaluable highnon important-
Musculoskeletal and connective tissue disorders TRAE (grade 3-4) 5.94 [0.70, 50.19]< 10%2 studies (2/-)5.2 %lownot evaluable highnon important-
Myalgia TRAE (grade 3-4) 1.91 [0.17, 21.35]< 10%2 studies (2/-)30.1 %lownot evaluable highnon important-
Myositis TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Nausea TRAE (grade 3-4) 1.28 [0.15, 11.02]< 10%3 studies (3/-)41.2 %lownot evaluable highnon important-
Nervous system disorders TRAE (grade 3-4) 2.53 [0.37, 17.24]< 10%2 studies (2/-)17.2 %lownot evaluable highnon important-
Neutropenia TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Pancreatitis TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Paraesthesia TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Peripheral neuropathy TRAE (grade 3-4) 0.64 [0.05, 8.40]< 10%2 studies (2/-)63.3 %lownot evaluable highnon important-
Pneumonitis TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Pruritus TRAE (grade 3-4) 0.32 [0.04, 2.41]< 10%3 studies (3/-)86.4 %lownot evaluable highnon important-
Pyrexia TRAE (grade 3-4) 0.33 [0.05, 2.28]< 10%3 studies (3/-)86.7 %lownot evaluable highnon important-
Rash TRAE (grade 3-4) 0.35 [0.13, 0.98]< 10%1 study (1/-)97.7 %NAnot evaluable non important-
Renal and urinary disorders TRAE (grade 3-4) 1.00 [0.02, 50.62]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Respiratory, thoracic and mediastinal disorders TRAE (grade 3-4) 0.36 [0.05, 2.74]< 10%3 studies (3/-)83.6 %lownot evaluable highnon important-
Sarcoidosis TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Skin and subcutaneous tissue disorders TRAE (grade 3-4) 0.22 [0.09, 0.52]< 10%3 studies (3/-)100.0 %lownot evaluable highnon important-
Stomatitis TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Thrombocytopenia TRAE (grade 3-4) 0.64 [0.05, 8.40]< 10%2 studies (2/-)63.3 %lownot evaluable highnon important-
Thyroiditis TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Uveitis TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Vitiligo TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Vomiting TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Weight decreased TRAE (grade 3-4) 0.95 [0.06, 15.31]< 10%2 studies (2/-)51.6 %lownot evaluable highnon 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.