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non squamous cell - mNSCLC - L1, anti-PD-(L)1 , 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) 0.74 [0.63, 0.86]< 161%6 studies (6/-)100.0 %some concernnot evaluable moderatecrucial-
deaths (OS) (extension) 0.59 [0.48, 0.71]< 10%2 studies (2/-)100.0 %lownot evaluable highimportant-
PFS (extension) 0.49 [0.41, 0.58]< 10%2 studies (2/-)100.0 %lownot evaluable highimportant-
progression or deaths (PFS) 0.63 [0.53, 0.74]< 178%7 studies (7/-)100.0 %some concernnot evaluable moderateimportant-
DOR 2.41 [1.27, 4.60]< 10%1 study (1/-)0.4 %NAnot evaluable non important-
objective responses (ORR) 2.03 [1.47, 2.80]> 182%7 studies (7/-)100.0 %some concernnot evaluable moderatenon important-
objective responses (ORR) (extension) 3.57 [2.52, 5.06]> 10%2 studies (2/-)100.0 %lownot evaluable highnon important-

safety endpoints 00

AE (any grade) 1.17 [0.33, 4.18]< 136%3 studies (3/-)40.7 %some concernnot evaluable moderatenon important-
AE (grade 3-4) 1.25 [0.94, 1.67]< 156%3 studies (3/-)6.5 %some concernnot evaluable moderatenon important-
AE leading to death (grade 5) 1.06 [0.72, 1.55]< 10%3 studies (3/-)38.6 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (any grade) 1.52 [1.17, 1.98]< 130%3 studies (3/-)0.1 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (grade 3-4) 2.04 [1.16, 3.59]< 10%1 study (1/-)0.7 %NAnot evaluable non important-
SAE (any grade) 1.52 [1.23, 1.89]< 10%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
STRAE (any grade) 1.86 [1.24, 2.77]< 147%3 studies (3/-)0.1 %some concernnot evaluable moderatenon important-
STRAE (grade 3-4) 5.56 [1.49, 20.67]< 10%1 study (1/-)0.5 %NAnot evaluable non important-
TRAE (any grade) 1.19 [0.63, 2.22]< 147%3 studies (3/-)29.9 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 1.57 [1.27, 1.93]< 10%3 studies (3/-)0.0 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 1.33 [0.61, 2.88]< 10%3 studies (3/-)23.8 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 0.76 [0.25, 2.35]< 10%1 study (1/-)68.0 %NAnot evaluable non important-
TRAE leading to discontinuation (grade 3-4) 4.44 [0.48, 40.91]< 10%1 study (1/-)9.6 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Acute kidney injury TRAE (grade 3-4) 4.32 [0.19, 97.73]< 10%1 study (1/-)18.2 %NAnot evaluable non important-
Adrenal insufficiency TRAE (grade 3-4) 0.71 [0.10, 5.03]< 10%2 studies (2/-)63.5 %some concernnot evaluable moderatenon important-
Alopecia TRAE (grade 3-4) 0.80 [0.08, 7.74]< 10%3 studies (3/-)57.5 %some concernnot evaluable moderatenon important-
Anaemia TRAE (grade 3-4) 1.30 [0.89, 1.90]< 122%3 studies (3/-)8.5 %some concernnot evaluable moderatenon important-
Arthralgia TRAE (grade 3-4) 0.75 [0.17, 3.37]< 10%1 study (1/-)64.6 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.76 [0.24, 2.44]< 148%2 studies (2/-)67.5 %some concernnot evaluable moderatenon important-
Blood creatinine increased TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 2.63 [0.62, 11.13]< 10%2 studies (2/-)9.5 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 1.01 [0.12, 8.66]< 10%3 studies (3/-)49.7 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 1.23 [0.43, 3.48]< 10%3 studies (3/-)34.8 %some concernnot evaluable moderatenon important-
Diabetes TRAE (grade 3-4) 1.00 [0.08, 13.05]< 10%2 studies (2/-)50.0 %lownot evaluable highnon important-
Diarrhoea TRAE (grade 3-4) 1.71 [0.46, 6.33]< 153%3 studies (3/-)21.2 %some concernnot evaluable moderatenon important-
Dizziness TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Dysgeusia TRAE (grade 3-4) 0.72 [0.04, 11.54]< 10%2 studies (2/-)59.2 %some concernnot evaluable moderatenon 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) 1.16 [0.70, 1.94]< 10%3 studies (3/-)28.1 %some concernnot evaluable moderatenon important-
Febrile neutropenia TRAE (grade 3-4) 1.49 [0.87, 2.57]< 10%2 studies (2/-)7.5 %some concernnot evaluable moderatenon important-
Hepatitis TRAE (grade 3-4) 5.70 [0.71, 45.75]< 10%2 studies (2/-)5.2 %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) 1.09 [0.13, 9.35]< 10%3 studies (3/-)46.9 %some concernnot evaluable moderatenon important-
Hypophysitis TRAE (grade 3-4) 1.10 [0.08, 14.41]< 10%2 studies (2/-)47.0 %some concernnot evaluable moderatenon important-
Hypothyroidism TRAE (grade 3-4) 1.70 [0.23, 12.33]< 10%3 studies (3/-)30.0 %some concernnot evaluable moderatenon important-
Increase AST TRAE (grade 3-4) 2.42 [0.43, 13.59]< 10%2 studies (2/-)15.9 %some concernnot evaluable moderatenon important-
Increased ALT TRAE (grade 3-4) 2.42 [0.43, 13.59]< 10%2 studies (2/-)15.9 %some concernnot evaluable moderatenon important-
Increased lacrimation (TRAE grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 1.45 [0.13, 16.15]< 10%2 studies (2/-)38.2 %lownot evaluable highnon important-
Leucopenia TRAE (grade 3-4) 1.81 [0.56, 5.78]< 10%2 studies (2/-)16.0 %some concernnot evaluable moderatenon important-
Myalgia TRAE (grade 3-4) 2.01 [0.18, 22.26]< 10%1 study (1/-)28.6 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 1.10 [0.08, 14.41]< 10%2 studies (2/-)47.0 %some concernnot evaluable moderatenon important-
Nausea TRAE (grade 3-4) 1.81 [0.92, 3.55]< 10%3 studies (3/-)4.3 %some concernnot evaluable moderatenon important-
Nephritis TRAE (grade 3-4) 3.81 [0.42, 34.44]< 10%2 studies (2/-)11.8 %lownot evaluable highnon important-
Neutropenia TRAE (grade 3-4) 1.24 [0.95, 1.62]< 10%3 studies (3/-)5.4 %some concernnot evaluable moderatenon important-
Pancreatitis TRAE (grade 3-4) 2.84 [0.32, 25.46]< 10%2 studies (2/-)17.7 %some concernnot evaluable moderatenon important-
Pancytopenia TRAE (grade 3-4) 0.52 [0.02, 15.84]< 10%1 study (1/-)64.4 %NAnot evaluable non 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) 1.23 [0.50, 3.01]< 10%1 study (1/-)32.4 %NAnot evaluable non important-
Peripheral oedema TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Pneumonia TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 1.53 [0.60, 3.89]< 10%3 studies (3/-)18.4 %lownot evaluable highnon important-
Pruritus TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 5.25 [0.57, 48.07]< 10%2 studies (2/-)7.2 %some concernnot evaluable moderatenon important-
Sepsis TRAE (grade 3-4) 2.06 [0.19, 22.93]< 10%2 studies (2/-)27.9 %some concernnot evaluable moderatenon important-
Severe skin reaction TRAE (grade 3-4) 1.01 [0.33, 3.06]< 10%2 studies (2/-)49.6 %lownot evaluable highnon important-
Stomatitis TRAE (grade 3-4) 2.22 [0.35, 14.07]< 10%2 studies (2/-)20.0 %some concernnot evaluable moderatenon important-
Thrombocytopenia TRAE (grade 3-4) 1.23 [0.79, 1.92]< 10%3 studies (3/-)18.5 %some concernnot evaluable moderatenon important-
Thyroiditis TRAE (grade 3-4) 0.50 [0.01, 25.20]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 1.36 [0.58, 3.21]< 10%3 studies (3/-)23.9 %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) 0.49 [0.01, 24.77]< 10%1 study (1/-)63.7 %NAnot evaluable non important-
Anaemia AE (grade 3-4) 1.30 [0.96, 1.76]< 111%2 studies (2/-)4.2 %some concernnot evaluable moderatenon important-
Arthralgia AE (grade 3-4) 7.97 [0.46, 139.30]< 10%1 study (1/-)8.0 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 1.73 [0.90, 3.32]< 10%2 studies (2/-)5.1 %lownot evaluable highnon important-
Back pain AE (grade 3-4) 3.97 [0.49, 31.97]< 10%1 study (1/-)9.9 %NAnot evaluable non 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) 2.78 [0.48, 16.08]< 10%2 studies (2/-)12.7 %lownot evaluable highnon important-
Cough AE (grade 3-4) 1.53 [0.14, 16.60]< 10%2 studies (2/-)36.4 %some concernnot evaluable moderatenon important-
Decreased appetite AE (grade 3-4) 1.24 [0.47, 3.25]< 10%2 studies (2/-)33.3 %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) 1.16 [0.58, 2.32]< 134%2 studies (2/-)33.8 %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) 0.49 [0.01, 24.77]< 10%1 study (1/-)63.7 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 1.77 [0.22, 14.12]< 184%2 studies (2/-)29.7 %lownot evaluable highnon 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) 1.55 [0.89, 2.70]< 15%2 studies (2/-)6.1 %some concernnot evaluable moderatenon important-
Febrile neutropenia AE (grade 3-4) 0.90 [0.33, 2.46]< 10%1 study (1/-)58.4 %NAnot evaluable non 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) 1.48 [0.30, 7.38]< 10%1 study (1/-)31.8 %NAnot evaluable non 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) 0.98 [0.24, 3.96]< 10%1 study (1/-)51.1 %NAnot evaluable non important-
Increased ALT AE (grade 3-4) 0.73 [0.20, 2.62]< 10%1 study (1/-)68.4 %NAnot evaluable non important-
Infusion-related reaction AE (grade 3-4) 0.98 [0.03, 29.35]< 10%1 study (1/-)50.4 %NAnot evaluable non important-
Lacrimation increased AE (grade 3-4) 0.50 [0.01, 25.20]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Leucopenia AE (grade 3-4) 1.57 [0.66, 3.73]< 10%1 study (1/-)15.4 %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.