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lung cancer : non small cell (NSCLC), atezolizumab 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) 0.81 [0.76, 0.87]< 10%8 studies (8/-)100.0 %some concernnot evaluable moderatecrucial-
deaths (OS) (extension) 0.76 [0.53, 1.08]< 10%1 study (1/-)93.7 %NAnot evaluable important-
PFS (extension) 0.72 [0.60, 0.86]< 10%1 study (1/-)100.0 %NAnot evaluable important-
progression or deaths (PFS) 0.73 [0.63, 0.84]< 182%9 studies (9/-)100.0 %some concernnot evaluable moderateimportant-
DOR 2.27 [1.44, 3.57]< 10%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
objective responses (ORR) 1.43 [1.15, 1.78]> 172%9 studies (9/-)99.9 %some concernnot evaluable moderatenon important-
objective responses (ORR) (extension) 1.68 [0.94, 3.01]> 10%1 study (1/-)95.9 %NAnot evaluable non important-

safety endpoints 00

AE (any grade) 0.82 [0.47, 1.42]< 144%6 studies (6/-)76.4 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 0.83 [0.52, 1.34]< 192%6 studies (6/-)77.9 %some concernnot evaluable moderatenon important-
AE leading to death (grade 5) 1.15 [0.77, 1.73]< 140%6 studies (6/-)24.5 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 0.82 [0.47, 1.43]< 192%6 studies (6/-)75.9 %some concernnot evaluable moderatenon important-
SAE (any grade) 1.44 [1.08, 1.94]< 172%5 studies (5/-)0.7 %some concernnot evaluable moderatenon important-
SAE (grade 3-4) 1.03 [0.80, 1.31]< 10%1 study (1/-)42.1 %NAnot evaluable non important-
STRAE (any grade) 1.38 [0.77, 2.47]< 186%4 studies (4/-)14.2 %some concernnot evaluable moderatenon important-
TRAE (any grade) 0.61 [0.30, 1.23]< 191%6 studies (6/-)91.6 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.58 [0.24, 1.38]< 197%6 studies (6/-)89.2 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 1.17 [0.60, 2.25]< 10%6 studies (6/-)32.5 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.07 [0.02, 0.29]< 10%1 study (1/-)100.0 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 1.32 [0.15, 11.35]< 10%2 studies (2/-)40.0 %some concernnot evaluable moderatenon important-
Alopecia TRAE (grade 3-4) 0.79 [0.08, 7.60]< 10%3 studies (3/-)58.1 %some concernnot evaluable moderatenon important-
Anaemia TRAE (grade 3-4) 1.27 [0.96, 1.68]< 125%3 studies (3/-)5.0 %some concernnot evaluable moderatenon important-
Arthralgia TRAE (grade 3-4) 0.78 [0.19, 3.17]< 10%2 studies (2/-)63.7 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 0.74 [0.39, 1.40]< 10%3 studies (3/-)82.1 %some concernnot evaluable moderatenon important-
Colitis TRAE (grade 3-4) 3.39 [0.92, 12.50]< 10%3 studies (3/-)3.3 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.77 [0.10, 5.99]< 10%3 studies (3/-)59.7 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 1.96 [0.71, 5.43]< 129%3 studies (3/-)9.8 %some concernnot evaluable moderatenon important-
Diabetes TRAE (grade 3-4) 3.12 [0.29, 33.74]< 10%2 studies (2/-)17.7 %some concernnot evaluable moderatenon important-
Diarrhoea TRAE (grade 3-4) 1.65 [0.72, 3.78]< 149%3 studies (3/-)11.9 %some concernnot evaluable moderatenon important-
Dysgeusia TRAE (grade 3-4) 0.49 [0.01, 24.77]< 10%1 study (1/-)63.7 %NAnot evaluable non important-
Epistaxis TRAE (grade 3-4) 8.09 [0.43, 153.59]< 10%1 study (1/-)8.4 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 1.27 [0.81, 1.99]< 10%3 studies (3/-)15.1 %some concernnot evaluable moderatenon important-
Febrile neutropenia TRAE (grade 3-4) 1.78 [1.04, 3.05]< 118%2 studies (2/-)1.7 %some concernnot evaluable moderatenon important-
Guillain-Barré syndrome TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 5.48 [1.30, 23.18]< 11%3 studies (3/-)1.1 %some concernnot evaluable moderatenon important-
Hypertension TRAE (grade 3-4) 1.00 [0.57, 1.78]< 10%1 study (1/-)49.6 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 1.62 [0.21, 12.58]< 10%3 studies (3/-)32.3 %some concernnot evaluable moderatenon important-
Hypophysitis TRAE (grade 3-4) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 2.18 [0.30, 15.78]< 10%3 studies (3/-)22.1 %some concernnot evaluable moderatenon important-
Increase AST TRAE (grade 3-4) 4.04 [0.45, 36.32]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 4.04 [0.45, 36.32]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 0.96 [0.06, 15.37]< 10%2 studies (2/-)51.2 %some concernnot evaluable moderatenon important-
Leucopenia TRAE (grade 3-4) 1.53 [0.83, 2.81]< 10%2 studies (2/-)8.7 %some concernnot evaluable moderatenon important-
Myalgia TRAE (grade 3-4) 1.66 [0.21, 12.91]< 10%2 studies (2/-)31.5 %some concernnot evaluable moderatenon important-
Myositis TRAE (grade 3-4) 1.49 [0.11, 19.42]< 10%2 studies (2/-)38.2 %some concernnot evaluable moderatenon important-
Nausea TRAE (grade 3-4) 2.00 [1.06, 3.77]< 10%3 studies (3/-)1.6 %some concernnot evaluable moderatenon important-
Nephritis TRAE (grade 3-4) 1.49 [0.11, 19.42]< 10%2 studies (2/-)38.2 %some concernnot evaluable moderatenon important-
Neutropenia TRAE (grade 3-4) 1.12 [0.90, 1.39]< 10%3 studies (3/-)15.1 %some concernnot evaluable moderatenon important-
Pancreatitis TRAE (grade 3-4) 2.93 [0.30, 28.98]< 10%2 studies (2/-)18.0 %some concernnot evaluable moderatenon important-
Paraesthesia TRAE (grade 3-4) 0.50 [0.02, 14.97]< 10%1 study (1/-)65.3 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 1.37 [0.62, 3.02]< 10%2 studies (2/-)21.8 %some concernnot evaluable moderatenon important-
Peripheral sensory neuropathy TRAE (grade 3-4) 4.04 [0.45, 36.31]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 2.31 [0.84, 6.37]< 10%3 studies (3/-)5.3 %some concernnot evaluable moderatenon important-
Rash TRAE (grade 3-4) 2.28 [0.63, 8.28]< 10%3 studies (3/-)10.6 %some concernnot evaluable moderatenon important-
Sepsis TRAE (grade 3-4) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Severe skin reaction TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 4.04 [0.45, 36.32]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 1.21 [0.85, 1.71]< 10%3 studies (3/-)14.7 %some concernnot evaluable moderatenon important-
Vomiting TRAE (grade 3-4) 1.48 [0.65, 3.36]< 10%3 studies (3/-)17.8 %some concernnot evaluable moderatenon important-

AE (grade 3-4) endpoints 00

hepatitis (Autoimmune) AE (grade 3-4) 0.98 [0.03, 29.35]< 10%1 study (1/-)50.4 %NAnot evaluable non important-
Abdominal pain AE (grade 3-4) 1.23 [0.24, 6.38]< 10%1 study (1/-)40.4 %NAnot evaluable non important-
Agranulocytosis (AE grade 3-4) 0.24 [0.01, 7.31]< 10%1 study (1/-)78.8 %NAnot evaluable non important-
Alopecia AE (grade 3-4) 0.48 [0.04, 6.27]< 10%2 studies (2/-)71.0 %some concernnot evaluable moderatenon important-
Anaemia AE (grade 3-4) 0.38 [0.08, 1.79]< 195%3 studies (3/-)88.9 %some concernnot evaluable moderatenon important-
Arthralgia AE (grade 3-4) 4.24 [0.72, 25.06]< 10%2 studies (2/-)5.6 %some concernnot evaluable moderatenon important-
Asthenia AE (grade 3-4) 0.77 [0.34, 1.74]< 136%3 studies (3/-)73.3 %some concernnot evaluable moderatenon important-
Back pain AE (grade 3-4) 2.09 [0.72, 6.04]< 10%2 studies (2/-)8.7 %some concernnot evaluable moderatenon important-
Blood creatinine increased AE (grade 3-4) 1.97 [0.09, 43.77]< 10%1 study (1/-)33.7 %NAnot evaluable non important-
Colitis AE (grade 3-4) 2.96 [0.15, 59.25]< 10%1 study (1/-)24.2 %NAnot evaluable non important-
Constipation AE (grade 3-4) 1.95 [0.54, 7.07]< 10%3 studies (3/-)15.6 %some concernnot evaluable moderatenon important-
Cough AE (grade 3-4) 2.15 [0.42, 11.13]< 10%3 studies (3/-)18.1 %some concernnot evaluable moderatenon important-
Decreased appetite AE (grade 3-4) 0.68 [0.18, 2.61]< 148%3 studies (3/-)71.5 %some concernnot evaluable moderatenon important-
Diabetes mellitus AE (grade 3-4) 1.97 [0.09, 43.77]< 10%1 study (1/-)33.7 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 0.62 [0.31, 1.23]< 115%3 studies (3/-)91.5 %some concernnot evaluable moderatenon important-
Dizziness AE (grade 3-4) 0.49 [0.03, 7.86]< 10%1 study (1/-)69.1 %NAnot evaluable non important-
Dry skin AE (grade 3-4) 0.24 [0.01, 7.31]< 10%1 study (1/-)78.8 %NAnot evaluable non important-
Dysgeusia AE (grade 3-4) 0.68 [0.04, 10.92]< 10%2 studies (2/-)60.6 %some concernnot evaluable moderatenon important-
Dyspnoea AE (grade 3-4) 2.20 [0.60, 8.13]< 156%3 studies (3/-)11.9 %some concernnot evaluable moderatenon important-
Epistaxis AE (grade 3-4) 0.49 [0.03, 7.86]< 10%1 study (1/-)69.1 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.81 [0.43, 1.54]< 144%3 studies (3/-)73.8 %some concernnot evaluable moderatenon important-
Febrile neutropenia AE (grade 3-4) 0.10 [0.00, 1.89]< 187%3 studies (3/-)93.6 %some concernnot evaluable moderatenon important-
Gastritis AE (grade 3-4) 1.97 [0.09, 43.77]< 10%1 study (1/-)33.7 %NAnot evaluable non important-
Headache AE (grade 3-4) 0.98 [0.03, 29.35]< 10%1 study (1/-)50.4 %NAnot evaluable non important-
Hypertension AE (grade 3-4) 1.00 [0.30, 3.31]< 10%2 studies (2/-)50.2 %some concernnot evaluable moderatenon important-
Hyperthyroidism AE (grade 3-4) 0.49 [0.03, 7.86]< 10%1 study (1/-)69.1 %NAnot evaluable non important-
Hypothyroidism AE (grade 3-4) 1.97 [0.09, 43.77]< 10%1 study (1/-)33.7 %NAnot evaluable non important-
Increase AST AE (grade 3-4) 1.71 [0.40, 7.37]< 129%2 studies (2/-)23.7 %some concernnot evaluable moderatenon important-
Increased ALT AE (grade 3-4) 1.49 [0.26, 8.74]< 152%2 studies (2/-)32.8 %some concernnot evaluable moderatenon important-
Infusion-related reaction AE (grade 3-4) 0.98 [0.03, 29.35]< 10%1 study (1/-)50.4 %NAnot evaluable non important-
Leucopenia AE (grade 3-4) 0.79 [0.13, 4.82]< 161%2 studies (2/-)60.2 %some concernnot evaluable moderatenon important-
Myalgia AE (grade 3-4) 0.36 [0.06, 2.27]< 10%2 studies (2/-)86.1 %some concernnot evaluable moderatenon important-
Nausea AE (grade 3-4) 1.04 [0.32, 3.45]< 143%3 studies (3/-)47.1 %some concernnot evaluable moderatenon important-
Neutropenia AE (grade 3-4) 0.12 [0.01, 2.04]< 196%3 studies (3/-)92.7 %some concernnot evaluable moderatenon important-
Pancytopenia (AE grade 3-4) 0.48 [0.10, 2.18]< 10%2 studies (2/-)83.0 %some concernnot evaluable moderatenon important-
Paraesthesia AE (grade 3-4) 1.97 [0.09, 43.77]< 10%1 study (1/-)33.7 %NAnot evaluable non important-
Peripheral neuropathy AE (grade 3-4) 0.29 [0.03, 2.86]< 148%2 studies (2/-)85.3 %some concernnot evaluable moderatenon important-
Peripheral oedema AE (grade 3-4) 0.53 [0.13, 2.16]< 10%2 studies (2/-)81.1 %some concernnot evaluable moderatenon important-
Peripheral sensory neuropathy AE (grade 3-4) 0.98 [0.24, 3.96]< 10%1 study (1/-)51.1 %NAnot evaluable non important-
Pneumonia AE (grade 3-4) 1.09 [0.57, 2.07]< 112%2 studies (2/-)40.1 %some concernnot evaluable moderatenon important-
Pneumonitis AE (grade 3-4) 0.24 [0.01, 7.31]< 10%1 study (1/-)78.8 %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.