Evidence map›Paper›PMID 26920887›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2016

Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer.

José Baselga, Gail D Lewis Phillips, Sunil Verma, Jungsil Ro, Jens Huober, Alice E Guardino, Meghna K Samant, Steve Olsen, Sanne L de Haas, Mark D Pegram

Erratum issuedOpen access · bronzeAbstract readClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 136 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 1 pooled it
10.9field-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

136 citing papers in PubMed, 1 synthesis or guideline pooled it, 225 citations in OpenAlex.

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  13. Biomarker analysis of the GATSBY study of trastuzumab emtansine versus a taxane in previously treated HER2-positive advanced gastric/gastroesophageal junction cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2019
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  17. PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015
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76 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 2 institutions in 2 countries.

José BaselgaMemorial Sloan Kettering Cancer Center, New York, New York. baselgaj@mskcc.org.
Gail D Lewis PhillipsGenentech, Inc., South San Francisco, California.
Sunil VermaSunnybrook Odette Cancer Centre, Toronto, Canada.
Jungsil RoNational Cancer Center, Goyang, Korea.
Jens HuoberBreast Center, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Alice E GuardinoGenentech, Inc., South San Francisco, California.
Meghna K SamantGenentech, Inc., South San Francisco, California.
Steve OlsenGenentech, Inc., South San Francisco, California.
Sanne L de HaasF. Hoffmann-La Roche Ltd, Basel, Switzerland.
Mark D PegramStanford Cancer Institute, Palo Alto, California.
Memorial Sloan Kettering Cancer Center · USRoche (Switzerland) · CH

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

purposeHER2-positive breast cancer is heterogeneous. Some tumors express mutations, like activating PIK3CA mutations or reduced PTEN expression, that negatively correlate with response to HER2-targeted therapies. In this exploratory analysis, we investigated whether the efficacy of trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprised of the cytotoxic agent DM1 linked to the HER2-targeted antibody trastuzumab, was correlated with the expression of specific biomarkers in the phase III EMILIA study. EXPERIMENTAL

designTumors were evaluated for HER2 (n = 866), EGFR (n = 832), and HER3 (n = 860) mRNA expression by quantitative reverse transcriptase PCR; for PTEN protein expression (n = 271) by IHC; and for PIK3CA mutations (n = 259) using a mutation detection kit. Survival outcomes were analyzed by biomarker subgroups. T-DM1 was also tested on cell lines and in breast cancer xenograft models containing PIK3CA mutations.

resultsLonger progression-free survival (PFS) and overall survival (OS) were observed with T-DM1 compared with capecitabine plus lapatinib in all biomarker subgroups. PIK3CA mutations were associated with shorter median PFS (mutant vs. wild type: 4.3 vs. 6.4 months) and OS (17.3 vs. 27.8 months) in capecitabine plus lapatinib-treated patients, but not in T-DM1-treated patients (PFS, 10.9 vs. 9.8 months; OS, not reached in mutant or wild type). T-DM1 showed potent activity in cell lines and xenograft models with PIK3CA mutations.

conclusionsAlthough other standard HER2-directed therapies are less effective in tumors with PI3KCA mutations, T-DM1 appears to be effective in both PI3KCA-mutated and wild-type tumors. Clin Cancer Res; 22(15); 3755-63. ©2016 AACR.

Indexed as

Biomarkers, TumorAdo-Trastuzumab EmtansineAnimalsAntineoplastic Agents, ImmunologicalBreast NeoplasmsDisease Models, AnimalErb-b2 Receptor Tyrosine KinasesFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMaytansineMiceNeoplasm MetastasisNeoplasm StagingPhosphatidylinositol 3-KinasesAdo-Trastuzumab EmtansineAntineoplastic Agents, ImmunologicalBiomarkers, TumorErb-b2 Receptor Tyrosine KinasesMaytansinePhosphatidylinositol 3-KinasesTrastuzumab

Identifiers

PMID26920887
PMCPMC5485412
OpenAlexW2286693725

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.