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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) 0.76 [0.56, 1.04]< 173%2 studies (2/-)95.6 %some concernnot evaluable moderatecrucial-
progression or deaths (PFS) 0.64 [0.51, 0.80]< 163%2 studies (2/-)100.0 %some concernnot evaluable moderateimportant-
DOR 2.14 [1.13, 4.04]< 10%1 study (1/-)1.0 %NAnot evaluable non important-
objective responses (ORR) 1.76 [1.14, 2.70]> 172%2 studies (2/-)99.5 %some concernnot evaluable moderatenon important-

safety endpoints 00

AE (any grade) 2.29 [0.55, 9.43]< 154%2 studies (2/-)12.7 %lownot evaluable highnon important-
AE (grade 3-4) 1.17 [0.85, 1.60]< 144%2 studies (2/-)17.2 %some concernnot evaluable moderatenon important-
AE leading to death (grade 5) 1.84 [0.95, 3.59]< 154%2 studies (2/-)3.6 %lownot evaluable highnon important-
AE leading to treatment discontinuation (any grade) 2.17 [1.63, 2.88]< 10%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
AE leading to treatment discontinuation (grade 3-4) 2.09 [1.28, 3.39]< 10%1 study (1/-)0.2 %NAnot evaluable non important-
SAE (any grade) 2.28 [1.66, 3.14]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
STRAE (any grade) 2.27 [1.46, 3.51]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
TRAE (any grade) 1.80 [0.98, 3.28]< 10%1 study (1/-)2.8 %NAnot evaluable non important-
TRAE (grade 3-4) 1.57 [1.14, 2.15]< 10%1 study (1/-)0.3 %NAnot evaluable non important-
TRAE leading to death (grade 5) 1.58 [0.68, 3.68]< 10%2 studies (2/-)14.6 %lownot evaluable highnon important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 2.00 [0.07, 59.91]< 10%1 study (1/-)34.7 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 1.09 [0.76, 1.58]< 10%1 study (1/-)31.9 %NAnot evaluable non important-
Arthralgia TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 0.77 [0.28, 2.10]< 10%1 study (1/-)69.3 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 8.08 [0.43, 153.53]< 10%1 study (1/-)8.4 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 0.50 [0.02, 14.93]< 10%1 study (1/-)65.3 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 3.41 [0.93, 12.49]< 10%1 study (1/-)3.3 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 6.05 [0.30, 121.16]< 10%1 study (1/-)12.2 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 1.44 [0.54, 3.83]< 10%1 study (1/-)23.2 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 1.89 [0.75, 4.80]< 10%1 study (1/-)9.0 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 2.66 [1.10, 6.46]< 10%1 study (1/-)1.5 %NAnot evaluable non 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) 1.00 [0.06, 16.05]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 2.00 [0.07, 59.91]< 10%1 study (1/-)34.7 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 4.02 [0.18, 89.44]< 10%1 study (1/-)19.3 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 1.46 [0.72, 2.93]< 10%1 study (1/-)14.7 %NAnot evaluable non important-
Myalgia TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 3.55 [0.73, 17.23]< 10%1 study (1/-)5.8 %NAnot evaluable non important-
Nephritis TRAE (grade 3-4) 1.00 [0.02, 50.55]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 0.93 [0.65, 1.35]< 10%1 study (1/-)64.6 %NAnot evaluable non important-
Pancreatitis TRAE (grade 3-4) 2.00 [0.07, 59.91]< 10%1 study (1/-)34.7 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 2.01 [0.37, 11.06]< 10%1 study (1/-)21.2 %NAnot evaluable non 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) 1.68 [0.40, 7.07]< 10%1 study (1/-)24.1 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 2.01 [0.18, 22.23]< 10%1 study (1/-)28.7 %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-
Thrombocytopenia TRAE (grade 3-4) 1.16 [0.68, 2.00]< 10%1 study (1/-)29.1 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 3.02 [0.31, 29.16]< 10%1 study (1/-)17.2 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

hepatitis (Autoimmune) AE (grade 3-4) 10.24 [0.56, 188.30]< 10%1 study (1/-)6.1 %NAnot evaluable non important-
Alopecia AE (grade 3-4) 0.33 [0.03, 3.22]< 10%1 study (1/-)82.7 %NAnot evaluable non important-
Anaemia AE (grade 3-4) 0.72 [0.46, 1.11]< 10%1 study (1/-)93.3 %NAnot evaluable non important-
Arthralgia AE (grade 3-4) 2.03 [0.37, 11.17]< 10%1 study (1/-)20.9 %NAnot evaluable non important-
Asthenia AE (grade 3-4) 0.60 [0.21, 1.66]< 10%1 study (1/-)83.9 %NAnot evaluable non important-
Colitis AE (grade 3-4) 2.04 [0.50, 8.23]< 10%1 study (1/-)16.0 %NAnot evaluable non important-
Constipation AE (grade 3-4) 0.67 [0.11, 4.04]< 10%1 study (1/-)66.9 %NAnot evaluable non important-
Cough AE (grade 3-4) 0.67 [0.11, 4.04]< 10%1 study (1/-)66.9 %NAnot evaluable non important-
Decreased appetite AE (grade 3-4) 1.21 [0.37, 4.02]< 10%1 study (1/-)37.6 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 1.88 [0.69, 5.16]< 10%1 study (1/-)11.0 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 3.04 [0.31, 29.44]< 10%1 study (1/-)17.0 %NAnot evaluable non important-
Epistaxis AE (grade 3-4) 1.01 [0.02, 50.94]< 10%1 study (1/-)49.9 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.82 [0.33, 2.01]< 10%1 study (1/-)66.9 %NAnot evaluable non important-
Hyperthyroidism AE (grade 3-4) 2.02 [0.07, 60.40]< 10%1 study (1/-)34.5 %NAnot evaluable non important-
Hypophysitis AE (grade 3-4) 4.05 [0.18, 90.23]< 10%1 study (1/-)19.1 %NAnot evaluable non important-
Hypothyroidism AE (grade 3-4) 2.02 [0.07, 60.40]< 10%1 study (1/-)34.5 %NAnot evaluable non important-
Infusion-related reaction AE (grade 3-4) 4.07 [0.45, 36.67]< 10%1 study (1/-)10.7 %NAnot evaluable non important-
Myalgia AE (grade 3-4) 2.02 [0.18, 22.43]< 10%1 study (1/-)28.5 %NAnot evaluable non important-
Nausea AE (grade 3-4) 0.75 [0.17, 3.39]< 10%1 study (1/-)64.4 %NAnot evaluable non important-
Neutropenia AE (grade 3-4) 0.90 [0.61, 1.32]< 10%1 study (1/-)70.9 %NAnot evaluable non important-
Peripheral neuropathy AE (grade 3-4) 1.52 [0.25, 9.15]< 10%1 study (1/-)32.6 %NAnot evaluable non important-
Pneumonitis AE (grade 3-4) 3.07 [0.61, 15.32]< 10%1 study (1/-)8.7 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 1.01 [0.14, 7.20]< 10%1 study (1/-)49.7 %NAnot evaluable non important-
Severe skin reactions AE (grade 3-4) 3.04 [0.31, 29.44]< 10%1 study (1/-)17.0 %NAnot evaluable non important-
Thrombocytopenia AE (grade 3-4) 1.07 [0.55, 2.08]< 10%1 study (1/-)42.4 %NAnot evaluable non important-
Thyroiditis AE (grade 3-4) 2.02 [0.07, 60.40]< 10%1 study (1/-)34.5 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 0.16 [0.02, 1.38]< 10%1 study (1/-)95.1 %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.