Evidence map›Paper›PMID 25355722›Full record

Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2015

Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA.

I E Krop, N U Lin, K Blackwell, E Guardino, J Huober, M Lu, D Miles, M Samant, M Welslau, V Diéras

Open access · bronzeAbstract readClinical Trial, Phase IIIComparative StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
201citing papers in PubMed, 7 pooled it
21.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

201 citing papers in PubMed, 7 syntheses or guidelines pooled it, 399 citations in OpenAlex.

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  3. DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2024
    Guideline
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  16. Chinese Society of Clinical Oncology breast cancer expert consensus on the diagnosis and treatment of breast cancer brain metastasis (2025).Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026
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141 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 5 countries.

I E KropDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston. Electronic address: ikrop@partners.org.
N U LinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston.
K BlackwellDepartment of Medicine, Duke University Medical Center, Durham.
E GuardinoProduct Development, Oncology, Genentech, Inc., South San Francisco, USA.
J HuoberDepartment of Medical Oncology and Breast Centre, Cantonal Hospital, St Gallen, Switzerland.
M LuProduct Development, Oncology, Genentech, Inc., South San Francisco, USA.
D MilesDepartment of Medical Oncology, Mount Vernon Cancer Centre, Northwood, UK.
M SamantBiostatistics, Genentech, Inc., South San Francisco, USA.
M WelslauHematology, Medical Office, Aschaffenburg, Germany.
V DiérasDepartment of Medical Oncology, Institut Curie, Paris, France.
Dana-Farber Cancer Institute · USDuke Medical Center · USInstitut Curie · FRKlinikum Aschaffenburg · DEMount Vernon Cancer Centre · GBUniversity of St. Gallen · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWe characterized the incidence of central nervous system (CNS) metastases after treatment with trastuzumab emtansine (T-DM1) versus capecitabine-lapatinib (XL), and treatment efficacy among patients with pre-existing CNS metastases in the phase III EMILIA study. PATIENTS AND

methodsIn EMILIA, patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer previously treated with trastuzumab and a taxane were randomized to T-DM1 or XL until disease progression. Patients with treated, asymptomatic CNS metastases at baseline and patients developing postbaseline CNS metastases were identified retrospectively by independent review; exploratory analyses were carried out.

resultsAmong 991 randomized patients (T-DM1 = 495; XL = 496), 95 (T-DM1 = 45; XL = 50) had CNS metastases at baseline. CNS progression occurred in 9 of 450 (2.0%) and 3 of 446 (0.7%) patients without CNS metastases at baseline in the T-DM1 and XL arms, respectively, and in 10 of 45 (22.2%) and 8 of 50 (16.0%) patients with CNS metastases at baseline. Among patients with CNS metastases at baseline, a significant improvement in overall survival (OS) was observed in the T-DM1 arm compared with the XL arm [hazard ratio (HR) = 0.38; P = 0.008; median, 26.8 versus 12.9 months]. Progression-free survival by independent review was similar in the two treatment arms (HR = 1.00; P = 1.000; median, 5.9 versus 5.7 months). Multivariate analyses demonstrated similar results. Grade ≥3 adverse events were reported in 48.8% and 63.3% of patients with CNS metastases at baseline administered T-DM1 and XL, respectively; no new safety signals were observed.

conclusionIn this retrospective, exploratory analysis, the rate of CNS progression in patients with HER2-positive advanced breast cancer was similar for T-DM1 and for XL, and higher overall in patients with CNS metastases at baseline compared with those without CNS metastases at baseline. In patients with treated, asymptomatic CNS metastases at baseline, T-DM1 was associated with significantly improved OS compared with XL.

Indexed as

Ado-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticAntineoplastic AgentsBreast NeoplasmsCapecitabineCentral Nervous System NeoplasmsDeoxycytidineDisease-Free SurvivalErb-b2 Receptor Tyrosine KinasesFemaleFluorouracilHumansAdo-Trastuzumab EmtansineAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticAntineoplastic AgentsCapecitabineDeoxycytidineERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesFluorouracilLapatinibMaytansineQuinazolinesTrastuzumabado-trastuzumab emtansinecentral nervous system metastasismetastatic breast cancerT-DM1

Identifiers

PMID25355722
PMCPMC4679405
OpenAlexW2125401809

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.