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renal cell cancer (RCC), pembrolizumab plus lenvatinib , 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) 0.66 [0.49, 0.88]< 10%1 study (1/-)99.7 %NAnot evaluable crucial-
progression or deaths (PFS) 0.39 [0.32, 0.48]< 10%1 study (1/-)100.0 %NAnot evaluable important-
objective responses (ORR) 1.97 [1.69, 2.29]> 10%1 study (1/-)100.0 %NAnot evaluable non important-

safety endpoints 00

AE (any grade) NaN [NaN, NaN]< 10%1 study (1/-)NaNNAnot evaluable non important-
AE (grade 3-4) 0.11 [0.05, 0.24]< 10%1 study (1/-)100.0 %NAnot evaluable non important-
AE leading to death (grade 5) 0.93 [0.42, 2.05]< 10%1 study (1/-)57.4 %NAnot evaluable non important-
AE leading to treatment discontinuation (any grade) 2.31 [1.58, 3.38]< 10%1 study (1/-)0.0 %NAnot evaluable non important-

AE (grade 3-4) endpoints 00

Arthralgia AE (grade 3-4) 4.88 [0.57, 42.03]< 10%1 study (1/-)7.6 %NAnot evaluable non important-
Constipation AE (grade 3-4) 5.84 [0.29, 116.96]< 10%1 study (1/-)12.7 %NAnot evaluable non important-
Decreased appetite AE (grade 3-4) 2.78 [0.99, 7.79]< 10%1 study (1/-)2.6 %NAnot evaluable non important-
Diarrhoea AE (grade 3-4) 1.91 [1.06, 3.46]< 10%1 study (1/-)1.6 %NAnot evaluable non important-
Dysgeusia AE (grade 3-4) 0.97 [0.06, 15.50]< 10%1 study (1/-)51.0 %NAnot evaluable non important-
Dysphonia AE (grade 3-4) 0.97 [0.02, 48.82]< 10%1 study (1/-)50.7 %NAnot evaluable non important-
Fatigue AE (grade 3-4) 0.96 [0.46, 2.00]< 10%1 study (1/-)53.9 %NAnot evaluable non important-
Hypertension AE (grade 3-4) 1.64 [1.15, 2.35]< 10%1 study (1/-)0.3 %NAnot evaluable non important-
Hypothyroidism AE (grade 3-4) 9.78 [0.53, 179.78]< 10%1 study (1/-)6.4 %NAnot evaluable non important-
Nausea AE (grade 3-4) 4.43 [0.95, 20.68]< 10%1 study (1/-)2.9 %NAnot evaluable non important-
Palmar–plantar erythrodysesthesia syndrome AE (grade 3-4) 1.04 [0.48, 2.25]< 10%1 study (1/-)45.8 %NAnot evaluable non important-
Proteinuria AE (grade 3-4) 2.74 [1.31, 5.76]< 10%1 study (1/-)0.4 %NAnot evaluable non important-
Rash AE (grade 3-4) 6.48 [1.45, 28.94]< 10%1 study (1/-)0.7 %NAnot evaluable non important-
Stomatitis AE (grade 3-4) 0.82 [0.27, 2.48]< 10%1 study (1/-)63.4 %NAnot evaluable non important-
Vomiting AE (grade 3-4) 2.36 [0.82, 6.79]< 10%1 study (1/-)5.5 %NAnot evaluable non important-
Weight decreased AE (grade 3-4) 29.30 [3.96, 216.58]< 10%1 study (1/-)0.0 %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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