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non squamous cell - mNSCLC - L2, immune chekpoint inhibitors , 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) 0.73 [0.59, 0.90]< 10%1 study (1/-)99.8 %NAnot evaluable crucial-
progression or deaths (PFS) 0.92 [0.77, 1.10]< 10%1 study (1/-)82.0 %NAnot evaluable important-
objective responses (ORR) 1.70 [1.11, 2.61]> 10%1 study (1/-)99.2 %NAnot evaluable non important-

safety endpoints 00

AE (any grade) 0.31 [0.20, 0.48]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
AE (grade 3-4) 0.42 [0.29, 0.59]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
STRAE (any grade) 0.32 [0.19, 0.55]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
STRAE (grade 3-4) 0.25 [0.14, 0.46]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
TRAE (grade 3-4) 0.10 [0.06, 0.16]< 10%1 study (1/-)100.0 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Acute kidney injury TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.13 [0.02, 1.07]< 10%1 study (1/-)97.1 %NAnot evaluable non important-
Arthralgia TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.15 [0.02, 1.28]< 10%1 study (1/-)95.8 %NAnot evaluable non important-
Blood creatinine increased TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 0.23 [0.01, 5.17]< 10%1 study (1/-)81.9 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 0.15 [0.01, 3.09]< 10%1 study (1/-)88.6 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 0.62 [0.10, 3.74]< 10%1 study (1/-)69.8 %NAnot evaluable non important-
Dysgeusia TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Eczema TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Erythema TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 0.21 [0.06, 0.74]< 10%1 study (1/-)99.2 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 0.02 [0.00, 0.27]< 10%1 study (1/-)99.8 %NAnot evaluable non important-
Hypersensitivity TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 0.47 [0.02, 13.95]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Increased lacrimation (TRAE grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 0.47 [0.02, 13.95]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 0.02 [0.00, 0.32]< 10%1 study (1/-)99.7 %NAnot evaluable non important-
Maculopapular rash TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Mucosal inflammation TRAE (grade 3-4) 0.09 [0.00, 1.69]< 10%1 study (1/-)94.4 %NAnot evaluable non important-
Myalgia TRAE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.93 [0.13, 6.67]< 10%1 study (1/-)52.7 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.00 [0.00, 0.08]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Palmar-plantar erythrodysaesthesia syndrome TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Paraesthesia TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 0.15 [0.01, 3.09]< 10%1 study (1/-)88.6 %NAnot evaluable non important-
Peripheral oedema TRAE (grade 3-4) 0.47 [0.02, 13.95]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 2.82 [0.29, 27.28]< 10%1 study (1/-)18.7 %NAnot evaluable non important-
Pruritic rash TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Pruritus generalised TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Pyrexia TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Skin exfoliation TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 0.23 [0.01, 5.17]< 10%1 study (1/-)81.9 %NAnot evaluable non important-
Thyroiditis TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Urticaria TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Abdominal pain AE (grade 3-4) 0.15 [0.01, 3.09]< 10%1 study (1/-)88.6 %NAnot evaluable non important-
Alopecia AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Anaemia AE (grade 3-4) 0.38 [0.13, 1.09]< 10%1 study (1/-)96.4 %NAnot evaluable non important-
Arthralgia AE (grade 3-4) 0.93 [0.13, 6.67]< 10%1 study (1/-)52.7 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 0.84 [0.35, 2.02]< 10%1 study (1/-)64.9 %NAnot evaluable non important-
Back pain AE (grade 3-4) 2.36 [0.45, 12.26]< 10%1 study (1/-)15.5 %NAnot evaluable non important-
Constipation AE (grade 3-4) 0.93 [0.13, 6.67]< 10%1 study (1/-)52.7 %NAnot evaluable non important-
Cough AE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Decreased appetite AE (grade 3-4) 1.17 [0.31, 4.40]< 10%1 study (1/-)40.8 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 0.93 [0.19, 4.66]< 10%1 study (1/-)53.3 %NAnot evaluable non important-
Dizziness AE (grade 3-4) 0.93 [0.06, 15.00]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Dry skin AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Dysgeusia AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 1.32 [0.58, 3.03]< 10%1 study (1/-)25.4 %NAnot evaluable non important-
Erythema AE (grade 3-4) 0.47 [0.02, 13.95]< 10%1 study (1/-)66.8 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.45 [0.20, 1.02]< 10%1 study (1/-)97.2 %NAnot evaluable non important-
Febrile neutropenia AE (grade 3-4) 0.01 [0.00, 0.24]< 10%1 study (1/-)99.8 %NAnot evaluable non important-
Headache AE (grade 3-4) 3.75 [0.17, 83.63]< 10%1 study (1/-)20.5 %NAnot evaluable non important-
Hypothyroidism AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Increased ALT AE (grade 3-4) 0.93 [0.06, 15.00]< 10%1 study (1/-)51.9 %NAnot evaluable non important-
Lacrimation increased AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Leucopenia AE (grade 3-4) 0.02 [0.00, 0.31]< 10%1 study (1/-)99.7 %NAnot evaluable non important-
Mucosal inflammation AE (grade 3-4) 0.18 [0.02, 1.58]< 10%1 study (1/-)93.7 %NAnot evaluable non important-
Myalgia AE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Nausea AE (grade 3-4) 2.36 [0.45, 12.26]< 10%1 study (1/-)15.5 %NAnot evaluable non important-
Neutropenia AE (grade 3-4) 0.01 [0.00, 0.07]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
Oropharyngeal pain AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Paraesthesia AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Peripheral neuropathy AE (grade 3-4) 0.15 [0.01, 3.09]< 10%1 study (1/-)88.6 %NAnot evaluable non important-
Peripheral oedema AE (grade 3-4) 0.93 [0.13, 6.67]< 10%1 study (1/-)52.7 %NAnot evaluable non important-
Pneumonia AE (grade 3-4) 0.65 [0.29, 1.50]< 10%1 study (1/-)84.1 %NAnot evaluable non important-
Pruritus AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Rash AE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Stomatitis AE (grade 3-4) 0.47 [0.04, 5.16]< 10%1 study (1/-)73.2 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 1.87 [0.06, 55.99]< 10%1 study (1/-)36.1 %NAnot evaluable non important-
Weight decreased AE (grade 3-4) 0.93 [0.02, 47.22]< 10%1 study (1/-)51.3 %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.



 

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