All patients
HER2 positive
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, HER inhibitor 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]
EGF100151, 2006 0.81 [0.65; 1.00]
EGF104900, 2010 0.74 [0.57; 0.96]
EMILIA, 2012 0.68 [0.55; 0.85]
HER2CLIMB, 2020 0.66 [0.50; 0.88]
LUX-Breast 1, 2016 1.48 [1.12; 1.95]
NALA, 2020 0.88 [0.72; 1.07]
NALA (brain metastases), 2020 0.90 [0.59; 1.38]
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]
0.82 [0.73 ; 0.93 ] AVEREL, 2013, CLEOPATRA, 2012, EGF100151, 2006, EGF104900, 2010, EMILIA, 2012, HER2CLIMB, 2020, LUX-Breast 1, 2016, NALA, 2020, NALA (brain metastases), 2020, NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012, SOPHIA, 2021, SYSUCC-002, 2022 12 62% 5,909 moderate low 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]
EMILIA, 2012 0.75 [0.64; 0.88]
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 [0.68 ; 0.83 ] ALTTO (T plus L vs T), 2020, CLEOPATRA, 2012, EMILIA, 2012, NeoALTTO (lapatinib plus trastuzumab vs trastuzumab), 2012, NeoALTTO (lapatinib vs trastuzumab), 2012 5 0% 6,593 moderate not evaluable iDFSdetailed results ExteNET, 2016 0.67 [0.50; 0.90]
0.67 [0.50 ; 0.90 ] ExteNET, 2016 1 0% 2,840 NA 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]
EGF104900, 2010 0.74 [0.58; 0.94]
EMILIA, 2012 0.65 [0.55; 0.77]
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]
NALA, 2020 0.76 [0.63; 0.92]
NALA (brain metastases), 2020 0.66 [0.41; 1.06]
SOPHIA, 2021 0.76 [0.59; 0.98]
SYSUCC-002, 2022 0.88 [0.71; 1.09]
0.72 [0.64 ; 0.82 ] AVEREL, 2013, CLEOPATRA, 2012, EGF104900, 2010, EMILIA, 2012, HER2CLIMB, 2020, HER2CLIMB (patients with brain metastases), 2020, LUX-Breast 1, 2016, NALA, 2020, NALA (brain metastases), 2020, SOPHIA, 2021, SYSUCC-002, 2022 11 67% 5,448 moderate low RFS/DFSdetailed results ALTTO (T plus L vs T), 2020 0.84 [0.70; 1.01]
ExteNET, 2016 0.63 [0.47; 0.85]
0.75 [0.57 ; 0.98 ] ALTTO (T plus L vs T), 2020, ExteNET, 2016 2 60% 7,030 moderate not evaluable DORdetailed results NALA, 2020 0.50 [0.33; 0.75]
NALA (brain metastases), 2020 0.47 [0.12; 1.88]
0.50 [0.34 ; 0.73 ] NALA, 2020, NALA (brain metastases), 2020 2 0% 722 moderate 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]
EGF100151, 2006 1.70 [0.96; 3.03]
EGF104900, 2010 1.56 [0.68; 3.59]
EMILIA, 2012 1.73 [1.29; 2.32]
LUX-Breast 1, 2016 1.04 [0.71; 1.52]
NALA (brain metastases), 2020 1.02 [0.37; 2.80]
SOPHIA, 2021 1.49 [0.96; 2.31]
1.74 [1.16 ; 2.59 ] AVEREL, 2013, CLEOPATRA, 2012, EGF100151, 2006, EGF104900, 2010, EMILIA, 2012, LUX-Breast 1, 2016, NALA (brain metastases), 2020, SOPHIA, 2021 8 80% 3,609 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 EGF100151, 2006 1.15 [0.59; 2.25]
HER2CLIMB, 2020 1.92 [0.77; 4.80]
1.38 [0.80 ; 2.36 ] EGF100151, 2006, HER2CLIMB, 2020 2 0% 917 moderate 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 NALA (brain metastases), 2020 0.48 [0.02; 14.79]
SOPHIA, 2021 0.76 [0.36; 1.59]
0.74 [0.36 ; 1.54 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate 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 NALA (brain metastases), 2020 0.31 [0.03; 3.12]
SOPHIA, 2021 1.21 [0.37; 4.03]
0.89 [0.29 ; 2.72 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 5% 629 moderate not evaluable Back pain AE (grade 3-4)detailed results NALA (brain metastases), 2020 0.98 [0.02; 50.38]
0.98 [0.02 ; 50.38 ] NALA (brain metastases), 2020 1 0% 99 NA not evaluable Constipation AE (grade 3-4)detailed results NALA (brain metastases), 2020 0.98 [0.02; 50.38]
SOPHIA, 2021 1.01 [0.14; 7.21]
1.00 [0.17 ; 5.83 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate 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 NALA (brain metastases), 2020 0.98 [0.06; 16.11]
SOPHIA, 2021 1.01 [0.06; 16.19]
0.99 [0.14 ; 7.14 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate not evaluable Diarrhoea AE (grade 3-4)detailed results NALA (brain metastases), 2020 2.48 [0.79; 7.77]
SOPHIA, 2021 1.01 [0.32; 3.17]
1.58 [0.65 ; 3.83 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 16% 629 moderate 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 NALA (brain metastases), 2020 0.98 [0.13; 7.24]
SOPHIA, 2021 1.67 [0.68; 4.10]
1.53 [0.67 ; 3.46 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate 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 NALA (brain metastases), 2020 0.98 [0.02; 50.38]
SOPHIA, 2021 1.01 [0.02; 50.97]
0.99 [0.06 ; 16.02 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate 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 NALA (brain metastases), 2020 0.64 [0.10; 4.00]
SOPHIA, 2021 3.05 [0.31; 29.47]
1.20 [0.27 ; 5.40 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 9% 629 moderate 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 Palmar–plantar erythrodysesthesia syndrome AE (grade 3-4)detailed results NALA (brain metastases), 2020 0.98 [0.29; 3.27]
0.98 [0.29 ; 3.27 ] NALA (brain metastases), 2020 1 0% 99 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 NALA (brain metastases), 2020 0.48 [0.02; 14.79]
SOPHIA, 2021 1.01 [0.06; 16.19]
0.75 [0.09 ; 6.50 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate not evaluable Rash AE (grade 3-4)detailed results NALA (brain metastases), 2020 0.48 [0.02; 14.79]
0.48 [0.02 ; 14.79 ] NALA (brain metastases), 2020 1 0% 99 NA not evaluable Stomatitis AE (grade 3-4)detailed results NALA (brain metastases), 2020 0.48 [0.02; 14.79]
SOPHIA, 2021 4.05 [0.18; 90.31]
1.55 [0.16 ; 15.45 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate not evaluable Vomiting AE (grade 3-4)detailed results NALA (brain metastases), 2020 0.98 [0.06; 16.11]
SOPHIA, 2021 0.50 [0.09; 2.75]
0.60 [0.14 ; 2.57 ] NALA (brain metastases), 2020, SOPHIA, 2021 2 0% 629 moderate not evaluable Weight decreased AE (grade 3-4)detailed results NALA (brain metastases), 2020 0.98 [0.06; 16.11]
0.98 [0.06 ; 16.11 ] NALA (brain metastases), 2020 1 0% 99 NA not evaluable 0.2 20.0 1.0 relative treatment effect www.metaEvidence.org 2024-06-03 10:20 +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: 712,429,903,472,969,902,1321,643,641,640,427,910,430,976,909,966,917,1013,1025,916,977,1029,1017,911,428,971,913,912,918,965,1067,978,915,914,973,974,702,1313,498,1314,368,1301,1412,1298,1299,1334,1332,1303,1325,1320,1305,1300,1429,1324,1335,1307,1322,1319,718,422,1304,421,1312,1326,1368,1373,1309,1302,1308
