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mML - 1st line (L1), atezolizumab plus SoC , 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) 0.85 [0.65, 1.12]< 10%1 study (1/-)87.6 %NAnot evaluable crucial-
progression or deaths (PFS) 0.78 [0.63, 0.97]< 10%1 study (1/-)98.8 %NAnot evaluable important-
objective responses (ORR) 1.19 [0.83, 1.71]> 10%1 study (1/-)82.7 %NAnot evaluable non important-

safety endpoints 00

AE leading to death (grade 5) 1.23 [0.42, 3.56]< 10%1 study (1/-)35.2 %NAnot evaluable non important-
AE leading to treatment discontinuation (any grade) 0.78 [0.47, 1.29]< 10%1 study (1/-)83.6 %NAnot evaluable non important-
STRAE (any grade) 1.24 [0.85, 1.81]< 10%1 study (1/-)12.9 %NAnot evaluable non important-
TRAE (any grade) 0.82 [0.11, 5.85]< 10%1 study (1/-)57.9 %NAnot evaluable non important-
TRAE (grade 3-4) 1.41 [0.93, 2.12]< 10%1 study (1/-)5.3 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Arthralgia TRAE (grade 3-4) 1.44 [0.48, 4.34]< 10%1 study (1/-)26.0 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 2.47 [0.45, 13.60]< 10%1 study (1/-)15.1 %NAnot evaluable non important-
Blood creatinine increased TRAE (grade 3-4) 0.61 [0.02, 18.27]< 10%1 study (1/-)61.1 %NAnot evaluable non important-
Chorioretinopathy TRAE (grade 3-4) 0.61 [0.02, 18.27]< 10%1 study (1/-)61.1 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 0.30 [0.01, 6.77]< 10%1 study (1/-)77.1 %NAnot evaluable non important-
Diarrhoea TRAE (grade 3-4) 0.53 [0.16, 1.76]< 10%1 study (1/-)84.8 %NAnot evaluable non important-
Dry skin TRAE (grade 3-4) 4.92 [0.22, 109.67]< 10%1 study (1/-)16.0 %NAnot evaluable non important-
Erythema TRAE (grade 3-4) 7.41 [0.37, 148.78]< 10%1 study (1/-)9.8 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 3.70 [0.38, 35.82]< 10%1 study (1/-)13.1 %NAnot evaluable non important-
Hyperthyroidism TRAE (grade 3-4) 4.92 [0.22, 109.67]< 10%1 study (1/-)16.0 %NAnot evaluable non important-
Increased lipase level TRAE (grade 3-4) 0.99 [0.64, 1.52]< 10%1 study (1/-)52.3 %NAnot evaluable non important-
Maculopapular rash TRAE (grade 3-4) 1.36 [0.78, 2.37]< 10%1 study (1/-)14.1 %NAnot evaluable non important-
Myalgia TRAE (grade 3-4) 2.46 [0.22, 27.26]< 10%1 study (1/-)23.4 %NAnot evaluable non important-
Nausea TRAE (grade 3-4) 0.17 [0.02, 1.40]< 10%1 study (1/-)94.9 %NAnot evaluable non important-
Peripheral oedema TRAE (grade 3-4) 1.22 [0.02, 61.84]< 10%1 study (1/-)46.1 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 4.92 [0.22, 109.67]< 10%1 study (1/-)16.0 %NAnot evaluable non important-
Pruritus TRAE (grade 3-4) 2.46 [0.22, 27.26]< 10%1 study (1/-)23.4 %NAnot evaluable non important-
Pyrexia TRAE (grade 3-4) 1.22 [0.24, 6.13]< 10%1 study (1/-)40.3 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 0.98 [0.53, 1.81]< 10%1 study (1/-)53.2 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 0.48 [0.09, 2.52]< 10%1 study (1/-)80.5 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Hypothyroidism AE (grade 3-4) 1.22 [0.02, 61.84]< 10%1 study (1/-)46.1 %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.



 

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