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es-BC - Triple negatif (TNBC) - (neo)adjuvant (NA), immune chekpoint inhibitors , 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) 0.69 [0.25, 1.89]< 10%1 study (1/-)76.5 %NAnot evaluable crucial-
deaths (OS) (extension) 0.24 [0.03, 2.28]< 10%1 study (1/-)89.2 %NAnot evaluable important-
events or deaths (EFS) 0.66 [0.48, 0.92]< 10%2 studies (2/-)99.3 %lownot evaluable highnon important-
pCR 3.30 [0.99, 11.04]> 193%3 studies (3/-)97.4 %lownot evaluable highnon important-

safety endpoints 00

AE (any grade) 0.33 [0.04, 3.09]< 10%2 studies (2/-)83.2 %lownot evaluable highnon important-
AE (grade 3-4) 1.27 [0.99, 1.62]< 10%2 studies (2/-)2.8 %lownot evaluable highnon important-
AE leading to death (grade 5) 0.97 [0.10, 9.43]< 10%2 studies (2/-)50.9 %lownot evaluable highnon important-
AE leading to treatment discontinuation (any grade) 1.18 [0.70, 2.01]< 10%1 study (1/-)26.7 %NAnot evaluable non important-
SAE (any grade) 1.36 [0.61, 3.02]< 174%2 studies (2/-)22.7 %lownot evaluable highnon important-
STRAE (any grade) 1.58 [0.91, 2.75]< 10%1 study (1/-)5.3 %NAnot evaluable non important-
TRAE (any grade) 0.51 [0.12, 2.15]< 10%2 studies (2/-)81.9 %lownot evaluable highnon important-
TRAE (grade 3-4) 1.23 [0.97, 1.55]< 10%2 studies (2/-)4.2 %lownot evaluable highnon important-
TRAE leading to death (grade 5) 1.50 [0.16, 14.43]< 10%1 study (1/-)36.5 %NAnot evaluable non important-
TRAE leading to discontinuation (any grade) 2.16 [1.53, 3.05]< 10%1 study (1/-)0.0 %NAnot evaluable non important-

TRAE (grade 3-4) endpoints 00

Adrenal insufficiency TRAE (grade 3-4) 4.58 [0.46, 45.81]< 10%2 studies (2/-)9.9 %lownot evaluable highnon important-
Alopecia TRAE (grade 3-4) 0.87 [0.36, 2.09]< 10%1 study (1/-)62.3 %NAnot evaluable non important-
Anaemia TRAE (grade 3-4) 1.27 [0.91, 1.77]< 10%1 study (1/-)8.1 %NAnot evaluable non important-
Asthenia TRAE (grade 3-4) 1.40 [0.65, 3.02]< 10%1 study (1/-)19.9 %NAnot evaluable non important-
Colitis TRAE (grade 3-4) 3.02 [0.51, 18.04]< 10%2 studies (2/-)11.3 %lownot evaluable highnon important-
Constipation TRAE (grade 3-4) 0.50 [0.01, 25.13]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Decreased appetite TRAE (grade 3-4) 3.51 [0.43, 28.62]< 10%1 study (1/-)12.2 %NAnot evaluable non important-
Diabetes TRAE (grade 3-4) 1.54 [0.14, 17.56]< 10%2 studies (2/-)36.5 %lownot evaluable highnon important-
Diarrhoea TRAE (grade 3-4) 1.71 [0.63, 4.67]< 10%1 study (1/-)14.8 %NAnot evaluable non important-
Dysgeusia TRAE (grade 3-4) 0.50 [0.01, 25.13]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Fatigue TRAE (grade 3-4) 2.29 [0.94, 5.58]< 10%1 study (1/-)3.5 %NAnot evaluable non important-
Febrile neutropenia TRAE (grade 3-4) 1.13 [0.82, 1.57]< 10%1 study (1/-)22.9 %NAnot evaluable non important-
Guillain-Barré syndrome TRAE (grade 3-4) 0.51 [0.02, 15.24]< 10%1 study (1/-)65.0 %NAnot evaluable non important-
Hepatitis TRAE (grade 3-4) 4.26 [0.42, 42.77]< 10%2 studies (2/-)11.1 %lownot evaluable highnon important-
Hyperthyroidism TRAE (grade 3-4) 1.54 [0.14, 17.56]< 10%2 studies (2/-)36.5 %lownot evaluable highnon important-
Hypophysitis TRAE (grade 3-4) 8.04 [0.46, 140.38]< 10%1 study (1/-)7.9 %NAnot evaluable non important-
Hypothyroidism TRAE (grade 3-4) 2.01 [0.19, 21.80]< 10%2 studies (2/-)28.4 %lownot evaluable highnon important-
Increase AST TRAE (grade 3-4) 9.67 [1.29, 72.54]< 10%1 study (1/-)1.4 %NAnot evaluable non important-
Increased ALT TRAE (grade 3-4) 2.34 [1.13, 4.86]< 10%1 study (1/-)1.1 %NAnot evaluable non important-
Infusion-related reactions TRAE (grade 3-4) 2.24 [0.82, 6.15]< 10%2 studies (2/-)5.8 %lownot evaluable highnon important-
Leucopenia TRAE (grade 3-4) 0.76 [0.57, 1.03]< 10%1 study (1/-)96.3 %NAnot evaluable non important-
Myocarditis TRAE (grade 3-4) 1.99 [0.09, 44.34]< 10%1 study (1/-)33.3 %NAnot evaluable non important-
Myositis TRAE (grade 3-4) 1.11 [0.09, 14.55]< 10%2 studies (2/-)46.7 %lownot evaluable highnon important-
Nausea TRAE (grade 3-4) 2.64 [1.01, 6.94]< 10%1 study (1/-)2.4 %NAnot evaluable non important-
Nephritis TRAE (grade 3-4) 7.03 [0.40, 124.15]< 10%1 study (1/-)9.4 %NAnot evaluable non important-
Neutropenia TRAE (grade 3-4) 1.06 [0.82, 1.38]< 10%1 study (1/-)31.6 %NAnot evaluable non important-
Pancreatitis TRAE (grade 3-4) 4.00 [0.21, 75.85]< 10%1 study (1/-)18.1 %NAnot evaluable non important-
Peripheral neuropathy TRAE (grade 3-4) 1.88 [0.62, 5.72]< 10%1 study (1/-)13.2 %NAnot evaluable non important-
Peripheral sensory neuropathy TRAE (grade 3-4) 1.20 [0.42, 3.43]< 10%1 study (1/-)36.8 %NAnot evaluable non important-
Pneumonitis TRAE (grade 3-4) 1.65 [0.25, 10.86]< 10%2 studies (2/-)30.3 %lownot evaluable highnon important-
Pyrexia TRAE (grade 3-4) 4.02 [0.50, 32.22]< 10%1 study (1/-)9.7 %NAnot evaluable non important-
Rash TRAE (grade 3-4) 1.37 [0.49, 3.84]< 12%2 studies (2/-)27.6 %lownot evaluable highnon important-
Sarcoidosis TRAE (grade 3-4) 0.50 [0.01, 25.13]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Severe skin reaction TRAE (grade 3-4) 6.86 [0.60, 79.02]< 132%2 studies (2/-)6.3 %lownot evaluable highnon important-
Stomatitis TRAE (grade 3-4) 11.10 [0.65, 189.37]< 10%1 study (1/-)5.0 %NAnot evaluable non important-
Thyroiditis TRAE (grade 3-4) 1.99 [0.09, 44.34]< 10%1 study (1/-)33.3 %NAnot evaluable non important-
Uveitis TRAE (grade 3-4) 0.50 [0.01, 25.13]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Vomiting TRAE (grade 3-4) 1.51 [0.59, 3.82]< 10%1 study (1/-)19.5 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

hepatitis (Autoimmune) AE (grade 3-4) 1.79 [0.06, 54.10]< 10%1 study (1/-)37.1 %NAnot evaluable non important-
Abdominal pain AE (grade 3-4) 0.65 [0.05, 8.46]< 10%2 studies (2/-)62.9 %lownot evaluable highnon important-
Alopecia AE (grade 3-4) 0.95 [0.06, 15.32]< 10%2 studies (2/-)51.4 %lownot evaluable highnon important-
Anaemia AE (grade 3-4) 1.15 [0.55, 2.43]< 10%2 studies (2/-)35.2 %lownot evaluable highnon important-
Arthralgia AE (grade 3-4) 1.54 [0.20, 12.07]< 10%2 studies (2/-)34.2 %some concernnot evaluable moderatenon important-
Asthenia AE (grade 3-4) 1.54 [0.25, 9.32]< 10%1 study (1/-)32.1 %NAnot evaluable non important-
Back pain AE (grade 3-4) 0.63 [0.05, 8.30]< 10%2 studies (2/-)63.5 %some concernnot evaluable moderatenon important-
Blood creatinine increased AE (grade 3-4) 0.05 [0.00, 0.89]< 10%1 study (1/-)97.8 %NAnot evaluable non important-
Constipation AE (grade 3-4) 0.71 [0.08, 6.14]< 10%2 studies (2/-)62.1 %some concernnot evaluable moderatenon important-
Cough AE (grade 3-4) 0.95 [0.06, 15.32]< 10%2 studies (2/-)51.4 %lownot evaluable highnon important-
Decreased appetite AE (grade 3-4) 1.02 [0.02, 51.63]< 10%1 study (1/-)49.6 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 4.58 [0.77, 27.06]< 10%2 studies (2/-)4.7 %lownot evaluable highnon important-
Dry skin AE (grade 3-4) 1.43 [0.11, 18.75]< 10%2 studies (2/-)39.3 %lownot evaluable highnon important-
Dysgeusia AE (grade 3-4) 1.02 [0.02, 51.63]< 10%1 study (1/-)49.6 %NAnot evaluable non important-
Dyspepsia AE (grade 3-4) 1.02 [0.02, 51.63]< 10%1 study (1/-)49.6 %NAnot evaluable non important-
Dyspnoea AE (grade 3-4) 0.99 [0.17, 5.78]< 10%2 studies (2/-)50.4 %lownot evaluable highnon important-
Epistaxis AE (grade 3-4) 0.95 [0.06, 15.32]< 10%2 studies (2/-)51.4 %lownot evaluable highnon important-
Fatigue AE (grade 3-4) 0.74 [0.29, 1.92]< 124%2 studies (2/-)73.2 %some concernnot evaluable moderatenon important-
Febrile neutropenia AE (grade 3-4) 1.32 [0.68, 2.57]< 10%2 studies (2/-)20.6 %lownot evaluable highnon important-
Headache AE (grade 3-4) 0.95 [0.09, 10.58]< 10%2 studies (2/-)51.6 %lownot evaluable highnon important-
Hypertension AE (grade 3-4) 0.84 [0.35, 2.00]< 10%1 study (1/-)65.4 %NAnot evaluable non important-
Hyperthyroidism AE (grade 3-4) 0.89 [0.02, 45.40]< 10%1 study (1/-)52.3 %NAnot evaluable non important-
Hypophysitis AE (grade 3-4) 1.79 [0.06, 54.10]< 10%1 study (1/-)37.1 %NAnot evaluable non important-
Hypothyroidism AE (grade 3-4) 0.89 [0.02, 45.40]< 10%1 study (1/-)52.3 %NAnot evaluable non important-
Increase AST AE (grade 3-4) 2.80 [0.81, 9.75]< 10%2 studies (2/-)5.3 %lownot evaluable highnon important-
Increased ALT AE (grade 3-4) 0.98 [0.44, 2.17]< 10%2 studies (2/-)51.9 %lownot evaluable highnon important-
Infusion-related reaction AE (grade 3-4) 0.97 [0.10, 9.43]< 10%2 studies (2/-)50.9 %lownot evaluable highnon important-
Injury, poisoning and procedure AE (grade 3-4) 0.89 [0.05, 14.46]< 10%1 study (1/-)53.2 %NAnot evaluable non important-
Lacrimation increased AE (grade 3-4) 1.02 [0.02, 51.63]< 10%1 study (1/-)49.6 %NAnot evaluable non important-
Leucopenia AE (grade 3-4) 1.17 [0.54, 2.51]< 151%2 studies (2/-)34.8 %some concernnot evaluable moderatenon important-
Mucosal inflammation AE (grade 3-4) 2.04 [0.07, 61.32]< 10%1 study (1/-)34.3 %NAnot evaluable non important-
Myalgia AE (grade 3-4) 1.86 [0.40, 8.67]< 10%2 studies (2/-)21.5 %some concernnot evaluable moderatenon important-
Nausea AE (grade 3-4) 0.20 [0.05, 0.79]< 10%2 studies (2/-)98.9 %lownot evaluable highnon important-
Neutropenia AE (grade 3-4) 0.98 [0.66, 1.45]< 10%2 studies (2/-)55.0 %lownot evaluable highnon important-
Oropharyngeal pain AE (grade 3-4) 2.04 [0.07, 61.32]< 10%1 study (1/-)34.3 %NAnot evaluable non important-
Paraesthesia AE (grade 3-4) 1.02 [0.02, 51.63]< 10%1 study (1/-)49.6 %NAnot evaluable non important-
Peripheral neuropathy AE (grade 3-4) 0.72 [0.31, 1.66]< 10%2 studies (2/-)78.0 %some concernnot evaluable moderatenon important-
Peripheral oedema AE (grade 3-4) 0.51 [0.02, 15.24]< 10%1 study (1/-)65.0 %NAnot evaluable non important-
Peripheral sensory neuropathy AE (grade 3-4) 1.28 [0.34, 4.86]< 10%1 study (1/-)35.8 %NAnot evaluable non important-
Pneumonitis AE (grade 3-4) 0.89 [0.02, 45.40]< 10%1 study (1/-)52.3 %NAnot evaluable non important-
Pruritus AE (grade 3-4) 0.25 [0.03, 2.26]< 10%1 study (1/-)89.0 %NAnot evaluable non important-
Pyrexia AE (grade 3-4) 4.11 [0.18, 91.86]< 10%1 study (1/-)18.9 %NAnot evaluable non important-
Rash AE (grade 3-4) 2.30 [0.41, 12.93]< 10%2 studies (2/-)17.4 %lownot evaluable highnon important-
Stomatitis AE (grade 3-4) 4.79 [0.55, 41.56]< 10%2 studies (2/-)7.9 %lownot evaluable highnon important-
Thrombocytopenia AE (grade 3-4) 0.44 [0.04, 4.94]< 10%1 study (1/-)74.6 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 1.43 [0.23, 8.88]< 10%2 studies (2/-)35.0 %lownot evaluable highnon 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.