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metastatic/advanced OC (mOC) - 2nd line (L2), avelumab based treatment , 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) 1.01 [0.79, 1.29]< 144%2 studies (2/-)47.3 %some concernnot evaluable moderatecrucial-
progression or deaths (PFS) 1.15 [0.54, 2.44]< 189%2 studies (2/-)35.9 %some concernnot evaluable moderateimportant-
DCR 2.37 [1.73, 3.25]> 112%2 studies (2/-)100.0 %some concernnot evaluable moderatenon important-
objective responses (ORR) 1.85 [0.49, 6.98]> 168%2 studies (2/-)81.9 %some concernnot evaluable moderatenon important-

safety endpoints 00

TRAE (any grade) 0.45 [0.26, 0.76]< 10%1 study (1/-)99.9 %NAnot evaluable non important-
TRAE (grade 3-4) 0.83 [0.21, 3.29]< 194%2 studies (2/-)60.5 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 0.72 [0.08, 6.23]< 10%2 studies (2/-)61.5 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.72 [0.40, 1.33]< 10%2 studies (2/-)85.2 %some concernnot evaluable moderatenon important-

TRAE (grade 3-4) endpoints 00

Abdominal pain TRAE (grade 3-4) 0.73 [0.08, 6.26]< 10%2 studies (2/-)61.3 %some concernnot evaluable moderatenon important-
Acute kidney injury TRAE (grade 3-4) 1.42 [0.11, 18.62]< 10%2 studies (2/-)39.4 %some concernnot evaluable moderatenon important-
Adrenal insufficiency TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Anaemia TRAE (grade 3-4) 0.48 [0.21, 1.09]< 10%2 studies (2/-)96.0 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 2.06 [0.30, 14.08]< 15%2 studies (2/-)23.1 %some concernnot evaluable moderatenon important-
Blood creatinine increased TRAE (grade 3-4) 1.42 [0.11, 18.62]< 10%2 studies (2/-)39.4 %some concernnot evaluable moderatenon important-
Colitis TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.96 [0.06, 15.40]< 10%2 studies (2/-)51.2 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Diarrhoea TRAE (grade 3-4) 4.92 [0.54, 44.97]< 10%2 studies (2/-)8.0 %some concernnot evaluable moderatenon important-
Dry skin TRAE (grade 3-4) 0.48 [0.04, 5.30]< 10%2 studies (2/-)72.5 %some concernnot evaluable moderatenon important-
Dyspnoea TRAE (grade 3-4) 1.42 [0.11, 18.62]< 10%2 studies (2/-)39.4 %some concernnot evaluable moderatenon important-
Fatigue TRAE (grade 3-4) 0.99 [0.05, 18.91]< 171%2 studies (2/-)50.4 %some concernnot evaluable moderatenon important-
Febrile neutropenia TRAE (grade 3-4) 0.25 [0.04, 1.51]< 10%2 studies (2/-)93.4 %some concernnot evaluable moderatenon important-
Hepatitis TRAE (grade 3-4) 1.42 [0.11, 18.62]< 10%2 studies (2/-)39.4 %some concernnot evaluable moderatenon important-
Hypersensitivity TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Hypertension TRAE (grade 3-4) 2.81 [0.28, 27.87]< 10%2 studies (2/-)19.0 %some concernnot evaluable moderatenon important-
Hyperthyroidism TRAE (grade 3-4) 1.42 [0.11, 18.62]< 10%2 studies (2/-)39.4 %some concernnot evaluable moderatenon important-
Increase AST TRAE (grade 3-4) 2.25 [0.20, 25.75]< 10%2 studies (2/-)25.8 %some concernnot evaluable moderatenon important-
Increased ALT TRAE (grade 3-4) 2.27 [0.20, 25.92]< 10%2 studies (2/-)25.6 %some concernnot evaluable moderatenon important-
Increased lipase level TRAE (grade 3-4) 2.82 [0.28, 27.94]< 10%2 studies (2/-)18.9 %some concernnot evaluable moderatenon important-
Infusion-related reactions TRAE (grade 3-4) 0.73 [0.08, 6.26]< 10%2 studies (2/-)61.3 %some concernnot evaluable moderatenon important-
Leucopenia TRAE (grade 3-4) 0.25 [0.04, 1.51]< 10%2 studies (2/-)93.4 %some concernnot evaluable moderatenon important-
Maculopapular rash TRAE (grade 3-4) 2.24 [0.25, 19.91]< 124%2 studies (2/-)23.5 %some concernnot evaluable moderatenon important-
Mucosal inflammation TRAE (grade 3-4) 0.66 [0.18, 2.48]< 10%2 studies (2/-)72.9 %some concernnot evaluable moderatenon important-
Nausea TRAE (grade 3-4) 1.68 [0.25, 11.08]< 10%2 studies (2/-)29.7 %some concernnot evaluable moderatenon important-
Neutropenia TRAE (grade 3-4) 0.30 [0.02, 5.18]< 173%2 studies (2/-)79.3 %some concernnot evaluable moderatenon important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 0.42 [0.01, 15.25]< 183%2 studies (2/-)68.1 %some concernnot evaluable moderatenon important-
Pancytopenia TRAE (grade 3-4) 0.24 [0.03, 2.14]< 10%2 studies (2/-)89.9 %some concernnot evaluable moderatenon important-
Peripheral neuropathy TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Peripheral oedema TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Pneumonia TRAE (grade 3-4) 1.92 [0.17, 21.31]< 10%2 studies (2/-)29.8 %some concernnot evaluable moderatenon important-
Pneumonitis TRAE (grade 3-4) 0.72 [0.08, 6.23]< 10%2 studies (2/-)61.5 %some concernnot evaluable moderatenon important-
Pruritic rash TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Pruritus TRAE (grade 3-4) 0.96 [0.06, 15.40]< 10%2 studies (2/-)51.2 %some concernnot evaluable moderatenon important-
Pyrexia TRAE (grade 3-4) 0.96 [0.06, 15.40]< 10%2 studies (2/-)51.2 %some concernnot evaluable moderatenon important-
Rash TRAE (grade 3-4) 1.03 [0.05, 21.89]< 172%2 studies (2/-)49.3 %some concernnot evaluable moderatenon important-
Sepsis TRAE (grade 3-4) 0.96 [0.06, 15.40]< 10%2 studies (2/-)51.2 %some concernnot evaluable moderatenon important-
Skin exfoliation TRAE (grade 3-4) 1.43 [0.11, 18.70]< 10%2 studies (2/-)39.3 %some concernnot evaluable moderatenon important-
Stomatitis TRAE (grade 3-4) 0.58 [0.03, 11.22]< 173%2 studies (2/-)63.8 %some concernnot evaluable moderatenon important-
Thrombocytopenia TRAE (grade 3-4) 0.48 [0.04, 5.30]< 10%2 studies (2/-)72.5 %some concernnot evaluable moderatenon important-
Vomiting TRAE (grade 3-4) 0.32 [0.06, 1.58]< 10%2 studies (2/-)91.9 %some concernnot evaluable moderatenon 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.