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Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.

2012· article· en· W4243385540 on OpenAlexaff
Kimberly Blackwell, David Miles, Luca Gianni, Ian E. Krop, Manfred Welslau, José Baselga, Mark D. Pegram, Do‐Youn Oh, Véronique Dièras, Steven R. Olsen, Liang Fang, Michael W. Lu, Ellie Guardino, Sunil Verma

Bibliographic record

VenueJournal of Clinical Oncology · 2012
Typearticle
Languageen
FieldMedicine
TopicHER2/EGFR in Cancer Research
Canadian institutionsUniversity of TorontoSunnybrook Health Science Centre
Fundersnot available
KeywordsMedicineTrastuzumab emtansineLapatinibCapecitabineTaxaneTrastuzumabMetastatic breast cancerInternal medicineInterim analysisAdverse effectGastroenterologyRefractory (planetary science)TolerabilityBreast cancerOncologyCancerClinical trial

Abstract

fetched live from OpenAlex

LBA1 Background: T-DM1 is an antibody-drug conjugate comprising T, a stable linker, and the potent cytotoxic agent DM1; it incorporates the antitumor activities of T and the HER2-targeted delivery of DM1. Methods: EMILIA is a randomized study of T-DM1 vs XL, the only approved combination for T-refractory HER2+ MBC. Patients (pts) received T-DM1 (3.6 mg/kg IV q3w) or X (1000 mg/m 2 PO bid, days 1–14 q3w) + L (1,250 mg PO daily) until progressive disease (PD) or unmanageable toxicity. Pts had confirmed HER2+ MBC (IHC3+ and/or FISH+), and prior therapy with T and a taxane. Primary end points were PFS by independent review, OS and safety. An interim OS analysis (efficacy boundary: HR= 0.617; p=0.0003) was planned at the time of the final PFS analysis. Results: 991 pts were enrolled; 978 received treatment. Median (med) durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) months (mo). Baseline demographics, prior therapy and disease characteristics were balanced. There was a significant improvement in PFS favoring T-DM1 (med 9.6 vs 6.4 mo; HR=0.650 [95% CI, 0.549–0.771]; p <0.0001). The med T-DM1 OS was not reached vs 23.3 mo (HR=0.621 [95% CI, 0.475–0.813]; p=0.0005); the interim efficacy boundary was not crossed. T-DM1 was well tolerated with no unexpected safety signals. The most common grade ≥3 adverse events (AEs) per treatment were for T-DM1: thrombocytopenia (12.9% vs 0.2%), increased AST (4.3% vs 0.8%), and increased ALT (2.9% vs 1.4%); for XL: diarrhea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0) and vomiting (4.5% vs 0.8%). The table lists other end points. Conclusions: T-DM1 conferred a significant and clinically meaningful improvement in PFS compared with XL. Other end points support T-DM1 as an active and well-tolerated novel therapy for HER2+ advanced BC. [Table: see text]

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.480
Threshold uncertainty score0.929

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0030.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.120
GPT teacher head0.484
Teacher spread0.364 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations42
Published2012
Admission routes1
Has abstractyes

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