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Record W3174706170 · doi:10.1016/j.ejca.2021.05.025

Preservation of quality of life in patients with human epidermal growth factor receptor 2–positive metastatic breast cancer treated with tucatinib or placebo when added to trastuzumab and capecitabine (HER2CLIMB trial)

2021· article· en· W3174706170 on OpenAlexaff
Volkmar Müller, Andrew Wardley, Elisavet Paplomata, Erika Hamilton, Amelia Zelnak, Louis Fehrenbacher, Erik Jakobsen, Elsa Curtit, Frances Boyle, Eva Brix, Andrew Brenner, Laurence Crouzet, Cristiano Ferrario, Montserrat Muñoz-Mateu, Hendrik-Tobias Arkenau, Nayyer Iqbal, Sramila Aithal, Margaret Block, Soeren Cold, Mathilde Cancel, Olwen Hahn, Teja Poosarla, Erica Stringer-Reasor, Marco Colleoni, David Cameron, Giuseppe Curigliano, Muriel Siadak, Kendra DeBusk, Jorge Ramos, Wentao Feng, Karen A. Gelmon

Bibliographic record

VenueEuropean Journal of Cancer · 2021
Typearticle
Languageen
FieldMedicine
TopicCancer Treatment and Pharmacology
Canadian institutionsSaskatchewan Cancer AgencyBC Cancer AgencyJewish General Hospital
FundersDaiichi Sankyo EuropeEMD SeronoGenentechEuropean Society for Medical OncologyEisaiSeagenG1 TherapeuticsMacroGenicsSilverback TherapeuticsPfizerNuCanaRegeneron PharmaceuticalsMylanUnum TherapeuticsHelsinn TherapeuticsAmgenRadius HealthSyndax PharmaceuticalsClovis OncologyTeva Pharmaceutical IndustriesHelsinnLes Laboratories Pierre FabreTaiho PharmaceuticalEli Lilly and CompanyAstraZenecaFoundation MedicineNational Cancer Research InstituteGenomic HealthMersana TherapeuticsKaryopharm TherapeuticsPuma Biotechnology
KeywordsCapecitabineTrastuzumabMetastatic breast cancerOncologyMedicineHuman Epidermal Growth Factor Receptor 2Internal medicinePlaceboBreast cancerCancerPathologyColorectal cancer

Abstract

fetched live from OpenAlex

AIMS: In HER2CLIMB, tucatinib significantly improved progression-free and overall survival in patients with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer. We evaluated the impact of tucatinib on health-related quality of life (HR-QoL) in HER2CLIMB. METHODS: Patients were randomised 2:1 to tucatinib or placebo combined with trastuzumab and capecitabine. Starting with protocol version 7, the EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire and EQ visual analogue scale (VAS) were administered at day 1 of cycle 1, every two cycles during cycles 3-9, every three cycles during cycle 12 and thereafter and at each patient's 30-day follow-up visit. RESULTS: Among 364 patients eligible for HR-QoL assessment, 331 (91%) completed ≥1 assessment. EQ-VAS scores were similar for both arms at baseline and maintained throughout treatment. EQ-5D-5L scores were similar between the treatment arms, stable throughout therapy and worsened after discontinuing treatment. Risk of meaningful deterioration (≥7 points) on EQ-VAS was reduced 19% in the tucatinib vs. placebo arm (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.55, 1.18); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.8 months (4.3, -) in the placebo arm. Among patients with brain metastases (n = 164), risk of meaningful deterioration on EQ-VAS was reduced 49% in the tucatinib arm (HR: 0.51; 95% CI: 0.28, 0.93); the median (95% CI) time to deterioration was not reached in the tucatinib arm and was 5.5 months (4.2, -) in the placebo arm. CONCLUSIONS: HR-QoL was preserved for patients with HER2+ metastatic breast cancer who were treated with tucatinib added to trastuzumab and capecitabine and maintained longer with tucatinib therapy than without it among those with brain metastases. CLINICAL TRIAL REGISTRATION: NCT02614794.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.010

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.001
Open science0.0000.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0030.000

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 head0.051
GPT teacher head0.344
Teacher spread0.294 · 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 source (direct Gemma or distilled Codex), 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".

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Citations13
Published2021
Admission routes1
Has abstractno

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