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metastatic/advanced NSCLC (mNSCLC) - 1st line (L1), Immune checkpoint association , 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) 0.86 [0.72, 1.03]< 166%4 studies (4/-)95.0 %some concernnot evaluable moderatecrucial-
deaths (OS) (extension) 0.66 [0.55, 0.80]< 10%1 study (1/-)100.0 %NAnot evaluable important-
PFS (extension) 0.68 [0.57, 0.82]< 10%1 study (1/-)100.0 %NAnot evaluable important-
progression or deaths (PFS) 0.82 [0.67, 1.00]< 171%5 studies (5/-)97.2 %some concernnot evaluable moderateimportant-
objective responses (ORR) 1.35 [0.99, 1.84]> 172%5 studies (5/-)97.1 %some concernnot evaluable moderatenon important-

safety endpoints 00

AE (any grade) 0.51 [0.27, 0.96]< 10%1 study (1/-)98.2 %NAnot evaluable non important-
AE (grade 3-4) 1.02 [0.76, 1.37]< 10%1 study (1/-)44.6 %NAnot evaluable non important-
AE leading to death (grade 5) 2.19 [1.17, 4.11]< 10%1 study (1/-)0.7 %NAnot evaluable non important-
AE leading to treatment discontinuation (any grade) 1.43 [0.97, 2.10]< 10%1 study (1/-)3.5 %NAnot evaluable non important-
AE leading to treatment discontinuation (grade 3-4) 2.14 [1.32, 3.47]< 10%1 study (1/-)0.1 %NAnot evaluable non important-
SAE (any grade) 1.93 [1.22, 3.04]< 10%1 study (1/-)0.2 %NAnot evaluable non important-
STRAE (any grade) 1.90 [1.55, 2.32]< 10%4 studies (4/-)0.0 %some concernnot evaluable moderatenon important-
STRAE (grade 3-4) 1.83 [1.47, 2.28]< 10%4 studies (4/-)0.0 %some concernnot evaluable moderatenon important-
TRAE (any grade) 0.78 [0.38, 1.62]< 191%4 studies (4/-)74.8 %some concernnot evaluable moderatenon important-
TRAE (grade 3-4) 0.94 [0.62, 1.42]< 183%4 studies (4/-)61.5 %some concernnot evaluable moderatenon important-
TRAE leading to death (grade 5) 1.25 [0.61, 2.53]< 10%3 studies (3/-)27.2 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (any grade) 2.62 [1.73, 3.95]< 161%4 studies (4/-)0.0 %some concernnot evaluable moderatenon important-
TRAE leading to discontinuation (grade 3-4) 3.56 [2.57, 4.94]< 10%4 studies (4/-)0.0 %some concernnot evaluable moderatenon important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 6.74 [0.82, 55.04]< 10%2 studies (2/-)3.8 %some concernnot evaluable moderatenon important-
Alopecia TRAE (grade 3-4) 0.95 [0.02, 47.95]< 10%1 study (1/-)51.0 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 0.17 [0.06, 0.46]< 169%4 studies (4/-)100.0 %some concernnot evaluable moderatenon important-
Asthenia TRAE (grade 3-4) 0.59 [0.21, 1.68]< 139%4 studies (4/-)83.8 %some concernnot evaluable moderatenon important-
Colitis TRAE (grade 3-4) 11.58 [1.50, 89.46]< 10%2 studies (2/-)1.0 %some concernnot evaluable moderatenon important-
Constipation TRAE (grade 3-4) 0.69 [0.11, 4.24]< 10%4 studies (4/-)65.6 %some concernnot evaluable moderatenon important-
Decreased appetite TRAE (grade 3-4) 0.84 [0.40, 1.79]< 10%4 studies (4/-)67.2 %some concernnot evaluable moderatenon important-
Diabetes TRAE (grade 3-4) 1.90 [0.06, 56.82]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 3.83 [1.72, 8.51]< 10%4 studies (4/-)0.0 %some concernnot evaluable moderatenon important-
Fatigue TRAE (grade 3-4) 1.46 [0.64, 3.34]< 129%4 studies (4/-)18.3 %some concernnot evaluable moderatenon important-
Febrile neutropenia TRAE (grade 3-4) 1.38 [0.60, 3.15]< 10%1 study (1/-)22.3 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 13.52 [0.76, 239.13]< 10%1 study (1/-)3.9 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 1.90 [0.06, 56.82]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Hypophysitis TRAE (grade 3-4) 1.90 [0.06, 56.82]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 2.72 [0.39, 19.13]< 10%3 studies (3/-)15.9 %some concernnot evaluable moderatenon important-
Increased ALT TRAE (grade 3-4) 2.46 [0.47, 12.75]< 10%1 study (1/-)14.3 %NAnot evaluable non important-
Increased lipase level TRAE (grade 3-4) 7.55 [2.24, 25.47]< 10%1 study (1/-)0.1 %NAnot evaluable non important-
Maculopapular rash TRAE (grade 3-4) 4.93 [0.57, 42.41]< 10%1 study (1/-)7.4 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.59 [0.20, 1.77]< 137%4 studies (4/-)82.7 %some concernnot evaluable moderatenon important-
Nephritis TRAE (grade 3-4) 0.95 [0.02, 47.95]< 10%1 study (1/-)51.0 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.05 [0.00, 0.74]< 184%4 studies (4/-)98.5 %some concernnot evaluable moderatenon important-
Pneumonitis TRAE (grade 3-4) 7.74 [0.96, 62.17]< 10%1 study (1/-)2.8 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 3.67 [0.73, 18.44]< 10%4 studies (4/-)5.8 %some concernnot evaluable moderatenon important-
Rash TRAE (grade 3-4) 5.99 [1.42, 25.24]< 10%4 studies (4/-)0.7 %some concernnot evaluable moderatenon important-
Thrombocytopenia TRAE (grade 3-4) 0.21 [0.01, 8.21]< 184%2 studies (2/-)79.4 %some concernnot evaluable moderatenon important-
Vomiting TRAE (grade 3-4) 0.26 [0.06, 1.14]< 156%4 studies (4/-)96.3 %some concernnot evaluable moderatenon important-

AE (grade 3-4) endpoints 00

Alopecia AE (grade 3-4) 0.95 [0.02, 47.95]< 10%1 study (1/-)51.0 %NAnot evaluable non important-
Anaemia AE (grade 3-4) 0.36 [0.04, 3.34]< 191%2 studies (2/-)81.4 %some concernnot evaluable moderatenon important-
Arthralgia AE (grade 3-4) 2.01 [0.36, 11.05]< 10%1 study (1/-)21.3 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 0.70 [0.29, 1.72]< 17%2 studies (2/-)77.9 %some concernnot evaluable moderatenon important-
Back pain AE (grade 3-4) 0.58 [0.14, 2.44]< 10%2 studies (2/-)77.1 %some concernnot evaluable moderatenon important-
Constipation AE (grade 3-4) 1.29 [0.28, 5.92]< 10%2 studies (2/-)37.1 %lownot evaluable highnon important-
Cough AE (grade 3-4) 0.66 [0.05, 8.56]< 10%2 studies (2/-)62.5 %lownot evaluable highnon important-
Decreased appetite AE (grade 3-4) 1.78 [0.55, 5.75]< 10%2 studies (2/-)16.7 %some concernnot evaluable moderatenon important-
Diarrhoea AE (grade 3-4) 3.61 [0.84, 15.63]< 144%2 studies (2/-)4.3 %some concernnot evaluable moderatenon important-
Dyspnoea AE (grade 3-4) 0.97 [0.46, 2.06]< 10%2 studies (2/-)52.8 %lownot evaluable highnon important-
Fatigue AE (grade 3-4) 1.38 [0.65, 2.91]< 10%2 studies (2/-)20.1 %some concernnot evaluable moderatenon important-
Hypothyroidism AE (grade 3-4) 1.00 [0.06, 16.01]< 10%1 study (1/-)50.1 %NAnot evaluable non important-
Increase AST AE (grade 3-4) 2.52 [0.48, 13.09]< 10%1 study (1/-)13.7 %NAnot evaluable non important-
Increased ALT AE (grade 3-4) 2.28 [0.69, 7.50]< 10%1 study (1/-)8.7 %NAnot evaluable non important-
Nausea AE (grade 3-4) 0.90 [0.21, 3.82]< 115%2 studies (2/-)55.4 %some concernnot evaluable moderatenon important-
Neutropenia AE (grade 3-4) 0.01 [0.00, 0.19]< 10%1 study (1/-)99.9 %NAnot evaluable non important-
Pneumonia AE (grade 3-4) 1.36 [0.72, 2.56]< 10%1 study (1/-)17.2 %NAnot evaluable non important-
Pneumonitis AE (grade 3-4) 2.21 [0.83, 5.91]< 10%1 study (1/-)5.6 %NAnot evaluable non important-
Pruritus AE (grade 3-4) 0.59 [0.08, 4.61]< 10%2 studies (2/-)69.1 %lownot evaluable highnon important-
Pyrexia AE (grade 3-4) 3.05 [0.28, 33.02]< 10%2 studies (2/-)18.1 %lownot evaluable highnon important-
Rash AE (grade 3-4) 3.86 [0.24, 62.86]< 149%2 studies (2/-)17.4 %some concernnot evaluable moderatenon important-
Thrombocytopenia AE (grade 3-4) 0.03 [0.00, 0.42]< 10%1 study (1/-)99.4 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 0.72 [0.03, 20.37]< 179%2 studies (2/-)57.5 %some concernnot evaluable moderatenon important-
Weight decreased AE (grade 3-4) 2.86 [0.30, 27.64]< 10%1 study (1/-)18.3 %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.