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non squamous - mNSCLC - L1 - Wild Type (WT), 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) 0.70 [0.54, 0.90]< 170%4 studies (4/-)99.7 %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) 0.58 [0.53, 0.64]< 10%5 studies (5/-)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) 2.38 [1.78, 3.19]> 159%5 studies (5/-)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) 4.04 [0.36, 44.82]< 10%1 study (1/-)13.0 %NAnot evaluable non important-
AE (grade 3-4) 1.03 [0.73, 1.45]< 10%1 study (1/-)44.4 %NAnot evaluable non important-
AE leading to death (grade 5) 1.13 [0.56, 2.28]< 10%1 study (1/-)36.6 %NAnot evaluable non important-
AE leading to treatment discontinuation (any grade) 2.19 [1.31, 3.65]< 10%1 study (1/-)0.1 %NAnot evaluable non 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-
STRAE (any grade) 3.47 [1.25, 9.62]< 10%1 study (1/-)0.8 %NAnot evaluable non important-
STRAE (grade 3-4) 5.56 [1.49, 20.67]< 10%1 study (1/-)0.5 %NAnot evaluable non important-
TRAE (any grade) 0.95 [0.29, 3.12]< 10%1 study (1/-)53.6 %NAnot evaluable non important-
TRAE (grade 3-4) 2.04 [0.92, 4.52]< 10%1 study (1/-)4.0 %NAnot evaluable non important-
TRAE leading to death (grade 5) 0.52 [0.05, 5.86]< 10%1 study (1/-)70.1 %NAnot evaluable non 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) 0.50 [0.03, 8.00]< 10%1 study (1/-)68.7 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.79 [0.27, 2.29]< 10%1 study (1/-)66.6 %NAnot evaluable non 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) 3.01 [0.15, 60.33]< 10%1 study (1/-)23.8 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 1.00 [0.03, 29.86]< 10%1 study (1/-)50.1 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 0.52 [0.02, 15.84]< 10%1 study (1/-)64.4 %NAnot evaluable non 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) 1.05 [0.02, 53.86]< 10%1 study (1/-)49.0 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 4.32 [0.19, 97.73]< 10%1 study (1/-)18.2 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 4.02 [0.21, 76.41]< 10%1 study (1/-)18.0 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 0.72 [0.04, 11.64]< 10%2 studies (2/-)59.0 %lownot evaluable highnon important-
Hypophysitis TRAE (grade 3-4) 0.50 [0.01, 25.20]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 1.56 [0.14, 17.88]< 10%2 studies (2/-)36.1 %lownot evaluable highnon important-
Increase AST TRAE (grade 3-4) 1.05 [0.06, 17.21]< 10%1 study (1/-)48.6 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 1.05 [0.06, 17.21]< 10%1 study (1/-)48.6 %NAnot evaluable non 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) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 0.50 [0.01, 25.20]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Nephritis TRAE (grade 3-4) 6.06 [0.34, 109.04]< 10%1 study (1/-)11.3 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 2.14 [0.19, 24.25]< 10%1 study (1/-)27.1 %NAnot evaluable non important-
Pancreatitis TRAE (grade 3-4) 2.00 [0.09, 44.56]< 10%1 study (1/-)33.3 %NAnot evaluable non important-
Pancytopenia TRAE (grade 3-4) 0.52 [0.02, 15.84]< 10%1 study (1/-)64.4 %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) 1.09 [0.35, 3.40]< 10%2 studies (2/-)44.4 %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) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Sepsis TRAE (grade 3-4) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non 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) 0.52 [0.02, 15.84]< 10%1 study (1/-)64.4 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 1.05 [0.14, 7.73]< 10%1 study (1/-)48.0 %NAnot evaluable non 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) 2.12 [0.07, 64.42]< 10%1 study (1/-)33.5 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Anaemia AE (grade 3-4) 1.07 [0.67, 1.71]< 10%1 study (1/-)38.2 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 1.83 [0.78, 4.31]< 10%1 study (1/-)8.3 %NAnot evaluable non important-
Constipation AE (grade 3-4) 2.00 [0.22, 18.06]< 10%1 study (1/-)26.9 %NAnot evaluable non important-
Cough AE (grade 3-4) 0.50 [0.01, 25.20]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Decreased appetite AE (grade 3-4) 3.02 [0.36, 25.28]< 10%1 study (1/-)15.5 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 1.79 [0.71, 4.50]< 10%1 study (1/-)10.9 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 0.67 [0.30, 1.48]< 10%1 study (1/-)83.9 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 2.37 [0.89, 6.34]< 10%1 study (1/-)4.3 %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-
Nausea AE (grade 3-4) 1.00 [0.40, 2.51]< 10%1 study (1/-)50.2 %NAnot evaluable non important-
Neutropenia AE (grade 3-4) 1.39 [0.84, 2.30]< 10%1 study (1/-)9.9 %NAnot evaluable non important-
Peripheral oedema AE (grade 3-4) 1.00 [0.03, 29.86]< 10%1 study (1/-)50.1 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 1.00 [0.03, 29.86]< 10%1 study (1/-)50.1 %NAnot evaluable non important-
Rash AE (grade 3-4) 1.17 [0.30, 4.56]< 10%1 study (1/-)41.3 %NAnot evaluable non important-
Thrombocytopenia AE (grade 3-4) 1.15 [0.60, 2.21]< 10%1 study (1/-)33.5 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 1.26 [0.48, 3.29]< 10%1 study (1/-)32.1 %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.