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mML - L2 - all population, ipilimumab plus gp100 , 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 [0.55, 1.27]< 186%2 studies (2/-)79.4 %lownot evaluable highcrucial-
DOR 0.68 [0.55, 0.85]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
objective responses (ORR) 1.28 [0.16, 9.97]> 185%2 studies (2/-)59.1 %lownot evaluable highnon important-

safety endpoints 00

AE (any grade) 1.96 [0.79, 4.84]< 10%2 studies (2/-)7.4 %lownot evaluable highnon important-
AE (grade 3-4) 0.97 [0.73, 1.28]< 10%2 studies (2/-)59.5 %lownot evaluable highnon important-
TRAE (any grade) 2.08 [1.43, 3.03]< 10%2 studies (2/-)0.0 %lownot evaluable highnon important-
TRAE (grade 3-4) 1.36 [0.91, 2.04]< 10%2 studies (2/-)6.7 %lownot evaluable highnon important-
TRAE leading to death (grade 5) 1.36 [0.28, 6.47]< 10%1 study (1/-)35.1 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 1.39 [0.15, 12.46]< 10%2 studies (2/-)38.6 %lownot evaluable highnon important-
Colitis TRAE (grade 3-4) 1.58 [0.12, 20.33]< 168%2 studies (2/-)36.4 %lownot evaluable highnon important-
Diarrhoea TRAE (grade 3-4) 1.59 [0.28, 9.13]< 161%2 studies (2/-)30.1 %lownot evaluable highnon important-
Endocrine disorders TRAE (grade 3-4) 0.59 [0.07, 5.18]< 151%2 studies (2/-)68.2 %lownot evaluable highnon important-
Gastrointestinal disorders TRAE (grade 3-4) 2.03 [0.20, 20.30]< 179%2 studies (2/-)27.6 %lownot evaluable highnon important-
Hepatitis TRAE (grade 3-4) 0.69 [0.06, 7.66]< 10%2 studies (2/-)61.7 %lownot evaluable highnon important-
Hepatobiliary disorders TRAE (grade 3-4) 0.71 [0.16, 3.24]< 112%2 studies (2/-)67.0 %lownot evaluable highnon important-
Hypophysitis TRAE (grade 3-4) 0.51 [0.10, 2.70]< 10%2 studies (2/-)78.5 %lownot evaluable highnon important-
Hypothyroidism TRAE (grade 3-4) 0.69 [0.06, 7.66]< 10%2 studies (2/-)61.7 %lownot evaluable highnon important-
Increase AST TRAE (grade 3-4) 0.27 [0.04, 1.95]< 10%2 studies (2/-)90.1 %lownot evaluable highnon important-
Increased ALT TRAE (grade 3-4) 1.39 [0.15, 12.46]< 10%2 studies (2/-)38.6 %lownot evaluable highnon important-
Pruritus TRAE (grade 3-4) 0.69 [0.06, 7.66]< 10%2 studies (2/-)61.7 %lownot evaluable highnon important-
Rash TRAE (grade 3-4) 2.22 [0.39, 12.59]< 10%2 studies (2/-)18.4 %lownot evaluable highnon important-
Skin and subcutaneous tissue disorders TRAE (grade 3-4) 2.15 [0.55, 8.37]< 10%2 studies (2/-)13.5 %lownot evaluable highnon important-
Vitiligo TRAE (grade 3-4) 0.35 [0.02, 5.54]< 10%2 studies (2/-)77.1 %lownot evaluable highnon important-

AE (grade 3-4) endpoints 00

Abdominal pain AE (grade 3-4) 0.47 [0.14, 1.62]< 140%2 studies (2/-)88.3 %lownot evaluable highnon important-
Anaemia AE (grade 3-4) 0.52 [0.18, 1.45]< 152%2 studies (2/-)89.5 %lownot evaluable highnon important-
Constipation AE (grade 3-4) 0.49 [0.13, 1.84]< 10%2 studies (2/-)85.3 %lownot evaluable highnon important-
Cough AE (grade 3-4) 0.69 [0.06, 7.66]< 10%2 studies (2/-)61.7 %lownot evaluable highnon important-
Decreased appetite AE (grade 3-4) 0.67 [0.25, 1.84]< 10%2 studies (2/-)78.0 %lownot evaluable highnon important-
Diarrhoea AE (grade 3-4) 1.82 [0.27, 12.37]< 168%2 studies (2/-)27.1 %lownot evaluable highnon important-
Dyspnoea AE (grade 3-4) 0.87 [0.43, 1.78]< 10%2 studies (2/-)64.3 %lownot evaluable highnon important-
Fatigue AE (grade 3-4) 1.01 [0.44, 2.31]< 134%2 studies (2/-)48.9 %lownot evaluable highnon important-
Headache AE (grade 3-4) 0.46 [0.16, 1.33]< 10%2 studies (2/-)92.5 %lownot evaluable highnon important-
Nausea AE (grade 3-4) 0.69 [0.26, 1.85]< 10%2 studies (2/-)77.1 %lownot evaluable highnon important-
Pyrexia AE (grade 3-4) 0.51 [0.10, 2.71]< 10%2 studies (2/-)78.4 %lownot evaluable highnon important-
Vomiting AE (grade 3-4) 0.80 [0.31, 2.11]< 10%2 studies (2/-)67.1 %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.