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non squamous - mNSCLC - L1 - all population, anti-PD-(L)1 versus bevacizumab plus carboplatin and paclitaxel, 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) 0.81 [0.70, 0.92]< 10%2 studies (2/-)99.9 %some concernnot evaluable moderatecrucial-
progression or deaths (PFS) 0.75 [0.50, 1.10]< 192%2 studies (2/-)92.9 %some concernnot evaluable moderateimportant-
objective responses (ORR) 1.41 [0.75, 2.66]> 190%2 studies (2/-)85.5 %some concernnot evaluable moderatenon important-

safety endpoints 00

AE (any grade) 0.49 [0.15, 1.65]< 10%1 study (1/-)87.3 %NAnot evaluable non important-
AE (grade 3-4) 1.14 [0.86, 1.52]< 10%1 study (1/-)18.0 %NAnot evaluable non important-
AE leading to death (grade 5) 1.10 [0.60, 2.03]< 10%1 study (1/-)37.5 %NAnot evaluable non important-
AE leading to treatment discontinuation (any grade) 1.46 [1.07, 1.99]< 10%1 study (1/-)0.9 %NAnot evaluable non important-
SAE (any grade) 1.40 [1.05, 1.87]< 10%1 study (1/-)1.1 %NAnot evaluable non important-
STRAE (any grade) 1.43 [1.02, 2.00]< 10%1 study (1/-)1.9 %NAnot evaluable non important-
TRAE (any grade) 0.81 [0.43, 1.53]< 10%1 study (1/-)74.4 %NAnot evaluable non important-
TRAE (grade 3-4) 1.38 [1.04, 1.83]< 10%1 study (1/-)1.2 %NAnot evaluable non important-
TRAE leading to death (grade 5) 1.23 [0.50, 3.01]< 10%1 study (1/-)32.4 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 1.00 [0.06, 16.09]< 10%1 study (1/-)49.9 %NAnot evaluable non important-
Alopecia TRAE (grade 3-4) 1.00 [0.02, 50.65]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 1.05 [0.58, 1.89]< 10%1 study (1/-)43.7 %NAnot evaluable non 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) 0.45 [0.15, 1.30]< 10%1 study (1/-)92.9 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 2.53 [0.49, 13.10]< 10%1 study (1/-)13.6 %NAnot evaluable non important-
Constipation TRAE (grade 3-4) 1.00 [0.02, 50.65]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 4.04 [0.45, 36.32]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 1.00 [0.02, 50.65]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 5.64 [1.24, 25.63]< 10%1 study (1/-)1.3 %NAnot evaluable non 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) 1.31 [0.57, 3.03]< 10%1 study (1/-)26.2 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 1.48 [0.85, 2.57]< 10%1 study (1/-)8.2 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 8.09 [0.43, 153.59]< 10%1 study (1/-)8.4 %NAnot evaluable non 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) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Hypophysitis TRAE (grade 3-4) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Increase AST TRAE (grade 3-4) 4.04 [0.45, 36.32]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 4.04 [0.45, 36.32]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Leucopenia TRAE (grade 3-4) 1.77 [0.51, 6.09]< 10%1 study (1/-)18.4 %NAnot evaluable non 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) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 1.91 [0.80, 4.57]< 10%1 study (1/-)7.2 %NAnot evaluable non important-
Nephritis TRAE (grade 3-4) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 1.27 [0.83, 1.94]< 10%1 study (1/-)13.8 %NAnot evaluable non important-
Pancreatitis TRAE (grade 3-4) 4.03 [0.18, 89.56]< 10%1 study (1/-)19.2 %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-
Pneumonitis TRAE (grade 3-4) 3.04 [0.61, 15.15]< 10%1 study (1/-)8.8 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 10.14 [0.55, 186.27]< 10%1 study (1/-)6.1 %NAnot evaluable non important-
Sepsis TRAE (grade 3-4) 2.01 [0.07, 60.02]< 10%1 study (1/-)34.6 %NAnot evaluable non important-
Stomatitis TRAE (grade 3-4) 4.04 [0.45, 36.32]< 10%1 study (1/-)10.8 %NAnot evaluable non important-
Thrombocytopenia TRAE (grade 3-4) 0.94 [0.47, 1.89]< 10%1 study (1/-)56.8 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 1.21 [0.37, 3.99]< 10%1 study (1/-)37.9 %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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