Top evidence (RCT only, high risk of bias excluded)
Best available evidence (possibly low or very low)
All RCTs
All studies (RCT+OBS)
la/mBC - HER2 positive, trastuzumab based treatment vs. all, meta-analysis of study results Outcome TE 95% CI n k I2 ROB Pub. bias deaths (OS)detailed results AVEREL, 2013 0.94 [0.68; 1.30]
CLEOPATRA, 2012 0.66 [0.52; 0.84]
HER2CLIMB, 2020 0.66 [0.50; 0.88]
LUX-Breast 1, 2016 1.48 [1.12; 1.95]
NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012 0.62 [0.30; 1.27]
SOPHIA, 2021 0.89 [0.70; 1.14]
SYSUCC-002, 2022 0.82 [0.65; 1.04]
0.85 [0.68 ; 1.06 ] AVEREL, 2013, CLEOPATRA, 2012, HER2CLIMB, 2020, LUX-Breast 1, 2016, NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012, SOPHIA, 2021, SYSUCC-002, 2022 7 75% 3,581 moderate not evaluable deaths (OS) (extension)detailed results ALTTO (T plus L vs T), 2020 0.86 [0.70; 1.06]
CLEOPATRA, 2012 0.69 [0.58; 0.82]
NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012 0.72 [0.41; 1.27]
NeoALTTO (lapatinib vs trastuzumab), 2012 0.85 [0.49; 1.47]
0.76 [0.67 ; 0.86 ] ALTTO (T plus L vs T), 2020, CLEOPATRA, 2012, NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012, NeoALTTO (lapatinib vs trastuzumab), 2012 4 0% 5,602 low not evaluable PFS (extension)detailed results CLEOPATRA, 2012 0.69 [0.59; 0.81]
0.69 [0.59 ; 0.81 ] CLEOPATRA, 2012 1 0% 808 NA not evaluable progression or deaths (PFS)detailed results AVEREL, 2013 0.82 [0.65; 1.03]
CLEOPATRA, 2012 0.62 [0.51; 0.75]
HER2CLIMB, 2020 0.54 [0.42; 0.70]
HER2CLIMB (patients with brain metastases), 2020 0.48 [0.34; 0.68]
LUX-Breast 1, 2016 1.10 [0.86; 1.41]
SOPHIA, 2021 0.76 [0.59; 0.98]
SYSUCC-002, 2022 0.88 [0.71; 1.09]
0.73 [0.60 ; 0.88 ] AVEREL, 2013, CLEOPATRA, 2012, HER2CLIMB, 2020, HER2CLIMB (patients with brain metastases), 2020, LUX-Breast 1, 2016, SOPHIA, 2021, SYSUCC-002, 2022 7 78% 3,439 moderate not evaluable RFS/DFSdetailed results ALTTO (T plus L vs T), 2020 0.84 [0.70; 1.01]
0.84 [0.70 ; 1.01 ] ALTTO (T plus L vs T), 2020 1 0% 4,190 NA not evaluable events or deaths (EFS)detailed results NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012 0.78 [0.47; 1.29]
0.78 [0.47 ; 1.29 ] NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012 1 0% 301 NA not evaluable events or deaths (EFS) (extended)detailed results NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012 0.81 [0.52; 1.26]
NeoALTTO (lapatinib vs trastuzumab), 2012 0.98 [0.64; 1.51]
0.89 [0.66 ; 1.22 ] NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012, NeoALTTO (lapatinib vs trastuzumab), 2012 2 0% 604 moderate not evaluable objective responses (ORR)detailed results AVEREL, 2013 1.24 [0.81; 1.90]
CLEOPATRA, 2012 10.80 [5.29; 22.05]
LUX-Breast 1, 2016 1.04 [0.71; 1.52]
SOPHIA, 2021 1.49 [0.96; 2.31]
2.02 [0.93 ; 4.41 ] AVEREL, 2013, CLEOPATRA, 2012, LUX-Breast 1, 2016, SOPHIA, 2021 4 91% 2,129 moderate not evaluable pCR detailed results NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012 2.60 [1.49; 4.54]
NeoALTTO (lapatinib vs trastuzumab), 2012 0.78 [0.47; 1.30]
1.42 [0.44 ; 4.60 ] NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012, NeoALTTO (lapatinib vs trastuzumab), 2012 2 90% 604 moderate not evaluable AE leading to treatment discontinuation (any grade)detailed results HER2CLIMB, 2020 1.92 [0.77; 4.80]
1.92 [0.77 ; 4.80 ] HER2CLIMB, 2020 1 0% 601 NA not evaluable Abdominal pain AE (grade 3-4)detailed results SOPHIA, 2021 1.35 [0.30; 6.09]
1.35 [0.30 ; 6.09 ] SOPHIA, 2021 1 0% 530 NA not evaluable Alopecia AE (grade 3-4)detailed results SOPHIA, 2021 1.01 [0.02; 50.97]
1.01 [0.02 ; 50.97 ] SOPHIA, 2021 1 0% 530 NA not evaluable Anaemia AE (grade 3-4)detailed results SOPHIA, 2021 0.76 [0.36; 1.59]
0.76 [0.36 ; 1.59 ] SOPHIA, 2021 1 0% 530 NA not evaluable Arthralgia AE (grade 3-4)detailed results SOPHIA, 2021 0.50 [0.02; 15.05]
0.50 [0.02 ; 15.05 ] SOPHIA, 2021 1 0% 530 NA not evaluable Asthenia AE (grade 3-4)detailed results SOPHIA, 2021 1.21 [0.37; 4.03]
1.21 [0.37 ; 4.03 ] SOPHIA, 2021 1 0% 530 NA not evaluable Constipation AE (grade 3-4)detailed results SOPHIA, 2021 1.01 [0.14; 7.21]
1.01 [0.14 ; 7.21 ] SOPHIA, 2021 1 0% 530 NA not evaluable Cough AE (grade 3-4)detailed results SOPHIA, 2021 2.02 [0.07; 60.44]
2.02 [0.07 ; 60.44 ] SOPHIA, 2021 1 0% 530 NA not evaluable Decreased appetite AE (grade 3-4)detailed results SOPHIA, 2021 1.01 [0.06; 16.19]
1.01 [0.06 ; 16.19 ] SOPHIA, 2021 1 0% 530 NA not evaluable Diarrhoea AE (grade 3-4)detailed results SOPHIA, 2021 1.01 [0.32; 3.17]
1.01 [0.32 ; 3.17 ] SOPHIA, 2021 1 0% 530 NA not evaluable Dizziness AE (grade 3-4)detailed results SOPHIA, 2021 2.02 [0.07; 60.44]
2.02 [0.07 ; 60.44 ] SOPHIA, 2021 1 0% 530 NA not evaluable Dyspnoea AE (grade 3-4)detailed results SOPHIA, 2021 0.50 [0.12; 2.01]
0.50 [0.12 ; 2.01 ] SOPHIA, 2021 1 0% 530 NA not evaluable Fatigue AE (grade 3-4)detailed results SOPHIA, 2021 1.67 [0.68; 4.10]
1.67 [0.68 ; 4.10 ] SOPHIA, 2021 1 0% 530 NA not evaluable Febrile neutropenia AE (grade 3-4)detailed results SOPHIA, 2021 0.61 [0.25; 1.49]
0.61 [0.25 ; 1.49 ] SOPHIA, 2021 1 0% 530 NA not evaluable Headache AE (grade 3-4)detailed results SOPHIA, 2021 1.01 [0.02; 50.97]
1.01 [0.02 ; 50.97 ] SOPHIA, 2021 1 0% 530 NA not evaluable Hypertension AE (grade 3-4)detailed results SOPHIA, 2021 2.55 [0.49; 13.25]
2.55 [0.49 ; 13.25 ] SOPHIA, 2021 1 0% 530 NA not evaluable Increase AST AE (grade 3-4)detailed results SOPHIA, 2021 2.39 [0.61; 9.34]
2.39 [0.61 ; 9.34 ] SOPHIA, 2021 1 0% 530 NA not evaluable Increased ALT AE (grade 3-4)detailed results SOPHIA, 2021 1.26 [0.34; 4.76]
1.26 [0.34 ; 4.76 ] SOPHIA, 2021 1 0% 530 NA not evaluable Infusion-related reaction AE (grade 3-4)detailed results SOPHIA, 2021 8.17 [0.43; 155.30]
8.17 [0.43 ; 155.30 ] SOPHIA, 2021 1 0% 530 NA not evaluable Leucopenia AE (grade 3-4)detailed results SOPHIA, 2021 4.08 [0.45; 36.72]
4.08 [0.45 ; 36.72 ] SOPHIA, 2021 1 0% 530 NA not evaluable Mucosal inflammation AE (grade 3-4)detailed results SOPHIA, 2021 0.50 [0.02; 15.05]
0.50 [0.02 ; 15.05 ] SOPHIA, 2021 1 0% 530 NA not evaluable Nausea AE (grade 3-4)detailed results SOPHIA, 2021 3.05 [0.31; 29.47]
3.05 [0.31 ; 29.47 ] SOPHIA, 2021 1 0% 530 NA not evaluable Neutropenia AE (grade 3-4)detailed results SOPHIA, 2021 1.73 [1.08; 2.78]
1.73 [1.08 ; 2.78 ] SOPHIA, 2021 1 0% 530 NA not evaluable Peripheral neuropathy AE (grade 3-4)detailed results SOPHIA, 2021 0.33 [0.03; 3.23]
0.33 [0.03 ; 3.23 ] SOPHIA, 2021 1 0% 530 NA not evaluable Pneumonia AE (grade 3-4)detailed results SOPHIA, 2021 0.33 [0.07; 1.65]
0.33 [0.07 ; 1.65 ] SOPHIA, 2021 1 0% 530 NA not evaluable Pyrexia AE (grade 3-4)detailed results SOPHIA, 2021 1.01 [0.06; 16.19]
1.01 [0.06 ; 16.19 ] SOPHIA, 2021 1 0% 530 NA not evaluable Stomatitis AE (grade 3-4)detailed results SOPHIA, 2021 4.05 [0.18; 90.31]
4.05 [0.18 ; 90.31 ] SOPHIA, 2021 1 0% 530 NA not evaluable Vomiting AE (grade 3-4)detailed results SOPHIA, 2021 0.50 [0.09; 2.75]
0.50 [0.09 ; 2.75 ] SOPHIA, 2021 1 0% 530 NA not evaluable 0.2 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-06-02 22:38 +02:00
TE: relative treatment effect (measured by a risk ratio, an odds ratio or an hazard ratio depending on what is reported in the papers);
k: number of studies; n: total number of patients;
ROB: risk of bias (ROB 2.0); Pub. bias: publication bias; OBS: observational studies; RCT: randomized clinical trials
pathologies: 355,337,146,317
- treatments: 1299,1334,1332,1303,1325,1320,1305,1300,1429,1324,1335,1307,1322
