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Record W3042325035 · doi:10.1186/s13045-020-00929-8

Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy

2020· article· en· W3042325035 on OpenAlex
Jörge E. Cortes, Florian H. Heidel, Walter Fiedler, Benjamin D. Smith, Tadeusz Robak, Pau Montesinos, Anna Candoni, Brian Leber, Mikkael A. Sekeres, Daniel A. Pollyea, Roxanne Ferdinand, Weidong Wendy, Thomas O’Brien, Ashleigh O’Connell, Geoffrey Chan, Michael Heuser

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of Hematology & Oncology · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHedgehog Signaling Pathway Studies
Canadian institutionsHamilton Health SciencesJuravinski Hospital
FundersDaiichi Sankyo EuropeIncyteAgios PharmaceuticalsJazz PharmaceuticalsEuropean Hematology AssociationCelgeneGilead SciencesServierAriad PharmaceuticalsAmgenPfizerAstellas Pharma
KeywordsMedicineInternal medicineCytarabineHazard ratioMyeloid leukemiaClinical trialOncologyConfidence interval

Abstract

fetched live from OpenAlex

BACKGROUND: The phase 2 BRIGHT AML 1003 trial evaluated efficacy and safety of glasdegib + low-dose cytarabine (LDAC) in patients with acute myeloid leukemia ineligible for intensive chemotherapy. The multicenter, open-label study randomized patients to receive glasdegib + LDAC (n = 78) or LDAC alone (n = 38). The rate of complete remission (CR) was 19.2% in the glasdegib + LDAC arm versus 2.6% in the LDAC arm (P = 0.015). METHODS: This post hoc analysis determines whether the clinical benefits of glasdegib are restricted to patients who achieve CR, or if they extend to those who do not achieve CR. RESULTS: In patients who did not achieve CR, the addition of glasdegib to LDAC improved overall survival (OS) versus LDAC alone (hazard ratio = 0.63 [95% confidence interval, 0.41-0.98]; P = 0.0182; median OS, 5.0 vs 4.1 months). Additionally, more patients receiving glasdegib + LDAC achieved durable recovery of absolute neutrophil count (≥ 1000/μl, 45.6% vs 35.5%), hemoglobin (≥ 9 g/dl, 54.4% vs 38.7%), and platelets (≥ 100,000/μl, 29.8% vs 9.7%). Transfusion independence was achieved by 15.0% and 2.9% of patients receiving glasdegib + LDAC and LDAC alone, respectively. CONCLUSIONS: Collectively, these data suggest that there are clinical benefits with glasdegib in the absence of CR. TRIAL REGISTRATION: ClinicalTrials.gov NCT01546038 (March 7, 2012).

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.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.028
Threshold uncertainty score0.700

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.020
GPT teacher head0.313
Teacher spread0.293 · 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