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Abstract P5-18-04: Combination plinabulin+pegfilgrastim (Plin+Peg) had better toxicity management and health related quality-of-life (HrQoL) compared to Peg alone in early-stage breast cancer (BC) patients (pts) treated with taxotere, doxorubicin and cyclophosphamide (TAC)

2022· article· en· W4220954053 on OpenAlexaff
Douglas W. Blayney, Yvette Lelorier, Dominic Mitchell, Lan Huang, Ramon Mohanlal

Bibliographic record

VenueCancer Research · 2022
Typearticle
Languageen
FieldMedicine
TopicNeutropenia and Cancer Infections
Canadian institutionsUniversité de Montréal
Fundersnot available
KeywordsMedicineNeutropeniaCardiotoxicityInternal medicineHeart failureAnthracyclineToxicitySurgeryCancerBreast cancer

Abstract

fetched live from OpenAlex

Abstract Introduction TAC chemotherapy may have better survival outcomes than TC or AC, but is used less often likely because of toxicity and reduced HrQoL (Fujii Jama Oncol 2005; Martin Annals of Oncol 2006). Combination Plin+Peg is superior to Peg alone for the prevention of chemotherapy-induced-neutropenia (CIN): 68% vs 86% grade (Gr) 4 neutropenia with Plin+Peg vs Peg (P=0.0015). FN rate was 3.6% vs 6.3% for Plin+Peg vs Peg. Here we analyzed the mitigating effects of Plin on toxicity and HrQoL impacted by adjuvant TAC in BC pts also receiving Peg. Methods In the randomized, double-blinded trial PROTECTIVE-2 (NCT0329457), Stage I,II,III BC pts received TAC (T dose 75mg/m2, A dose 50 mg/m2, C dose 500 mg/m2) with either the Plin+Peg combination (n=110) or Peg alone (n=111) for 4 cycles. Toxicity was evaluated by central laboratory (Covance) hematology and chemistry assessments, AE collection and 12-lead ECG. HrQoL was assessed by EORTC QLQ-C30 and EQ-5D-5L. pCR rate was assessed by pathological evaluation of excised BC tissue after surgery. Pts with abnormal cardiac function meeting any of the following criteria were excluded: 1. Prior doxorubicin (>240 mg/m2) or anthracycline exposure; 2. Cardiac ventricular dysfunction; 3. LVEF≤50%; 4. Congestive heart failure of NYHA Class II,III, IV cardiac disease; 5. History of myocardial infarction or coronary artery disease; 6. ECG findings consistent with active ischemic heart disease; angina pectoris requiring medication; 7. Arrhythmia requiring medication; severe conduction anomaly; 8. History of congenital QT prolongation; 9. Significant cardiac valvular disease; 10. Uncontrolled hypertension. Plin 40 mg fixed dose was given on day 1 (the day of TAC administration), and peg 6mg was given on day 2. Results All grade (Gr) AE frequency was 97% vs 96% in Plin+Peg vs Peg. However a shift to lower grade was noted. Gr 4 AE frequency was lower with Plin+ Peg vs Peg: 59% vs 80% (p<0.03). Gr3 (18% vs 6%) and Gr 2 (19% vs 9%) frequency was higher with Plin+Peg vs Peg. EQ-5D-5L utility values over all cycles had slightly increased with Plin+Peg, but steadily decreased with Peg alone (see table); Day -1 represent the score on the date before TAC dosing. ⋯add more HrQoL data⋯.pCR rates was numerically higher with Plin+Peg vs Peg (13.04% vs 12.5%). No cardiac dysfunction-related AEs were noted with Plin+Peg or Peg. Conclusion The addition of Plin to Peg for CIN prevention enables better management of TAC induced toxicity and HrQoL. TAC should be reevaluated in early stage BC patients in light of the improved outcomes with Plin+Peg support. EQ-5D-5L Utility values*+Cycle 1 Day -1Cycle 2 Day -1Cycle 3 Day -1Cycle 4 Day -1Plin +Peg (n=109)0.930.950.930.92Peg (n=106)0.930.910.890.87*p=0.0245 for Plin+Peg vs Peg favoring Plin+Peg +United States Valuation of EQ-5D-5L Health States Using (Pickard 2019). Citation Format: Douglas W. Blayney, Yvette Lelorier, Dominic Mitchell, Lan Huang, Ramon Mohanlal. Combination plinabulin+pegfilgrastim (Plin+Peg) had better toxicity management and health related quality-of-life (HrQoL) compared to Peg alone in early-stage breast cancer (BC) patients (pts) treated with taxotere, doxorubicin and cyclophosphamide (TAC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-04.

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: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.019

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0060.000

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 head0.090
GPT teacher head0.395
Teacher spread0.305 · 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 designNon-randomized 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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Citations0
Published2022
Admission routes1
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