Meredith Buxton
A5051494466- Breast Cancer Treatment Studies
- HER2/EGFR in Cancer Research
- Advanced Breast Cancer Therapies
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- Statistical Methods in Clinical Trials
- COVID-19 Clinical Research Studies
- Sepsis Diagnosis and Treatment
- Long-Term Effects of COVID-19
- Radiomics and Machine Learning in Medical Imaging
- Glioma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Health Systems, Economic Evaluations, Quality of Life
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Venous Thromboembolism Diagnosis and Management
- Angiogenesis and VEGF in Cancer
- Lung Cancer Treatments and Mutations
- BRCA gene mutations in cancer
- Breast Lesions and Carcinomas
- Heart Failure Treatment and Management
- Estrogen and related hormone effects
- Gene expression and cancer classification
- HIV, Drug Use, Sexual Risk
- DNA Repair Mechanisms
University of California, San Francisco
2013-2024
Association Clinique et Thérapeutique Infantile du Val de Marne
2022-2023
Medical Research Institute of New Zealand
2023
University of Auckland
2023
Middlemore Hospital
2023
Auckland City Hospital
2023
Institute for Global Environmental Strategies
2022
University Health Network
2021
St. Michael's Hospital
2021
Health Sciences Centre
2021
Thrombosis and inflammation may contribute to morbidity mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill Covid-19.
<h3>Importance</h3> Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. <h3>Objective</h3> To determine whether hydrocortisone improves outcome patients with COVID-19. <h3>Design, Setting, and Participants</h3> An ongoing adaptive platform trial testing multiple interventions within therapeutic domains, example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 June 17, 2020, 614 adult suspected confirmed COVID-19 were enrolled...
Thrombosis and inflammation may contribute to the risk of death complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation improve outcomes in noncritically ill who are hospitalized Covid-19.In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned were Covid-19 not critically (which was defined as an absence critical care-level organ support at enrollment) receive pragmatically regimens either...
The genetic and clinical heterogeneity of breast cancer makes the identification effective therapies challenging. We designed I-SPY 2, a phase multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for cancer. goal is match responding subtypes. report results veliparib, poly(ADP-ribose) polymerase (PARP) inhibitor, combined carboplatin.In this ongoing trial, women are eligible participation if they have stage II...
The heterogeneity of breast cancer makes identifying effective therapies challenging. I-SPY 2 trial, a multicenter, adaptive phase trial neoadjuvant therapy for high-risk clinical stage II or III cancer, evaluated multiple new agents added to standard chemotherapy assess the effects on rates pathological complete response (i.e., absence residual in lymph nodes at time surgery).We used randomization compare plus tyrosine kinase inhibitor neratinib with control. Eligible women were categorized...
Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter study integrating clinical, imaging, genomic data evaluate pathologic response, RFS, their relationship predictability based on biomarkers.
Neoadjuvant chemotherapy for breast cancer allows individual tumor response to be assessed depending on molecular subtype, and judge the impact of therapy recurrence-free survival (RFS). The multicenter I-SPY 1 TRIAL evaluated patients with ≥3 cm tumors by using early imaging signatures, outcomes pathologic complete (pCR) RFS. current analysis was performed data from who had profiles did not receive trastuzumab. various classifiers tested were highly correlated. Categorization signatures...
BackgroundPrevious studies have independently validated the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. We used results from several independent cohorts in a pooled patient-level analysis to evaluate relationship RCB with long-term prognosis across different phenotypic subtypes breast cancer, assess generalisability broad range practice settings.MethodsIn this analysis, 12 institutes and trials Europe USA were identified by personal communications...
<h3>Importance</h3> Pathologic complete response (pCR) is a known prognostic biomarker for long-term outcomes. The I-SPY2 trial evaluated if the strength of this clinical association persists in context phase 2 neoadjuvant platform trial. <h3>Objective</h3> To evaluate pCR with event-free survival (EFS) and distant recurrence–free (DRFS) subpopulations women high-risk operable breast cancer treated standard therapy or one several novel agents. <h3>Design, Setting, Participants</h3>...
Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19.
Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity treatment effect (HTE) across individuals. Better understanding HTE could facilitate individualized decision-making. Objective To evaluate for and compare approaches assessing HTE. Design, Setting, Participants Exploratory analysis a multiplatform adaptive RCT vs usual care pharmacologic thromboprophylaxis 3320 enrolled...
The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin is a key pathway survival and therapeutic resistance in breast cancer. We evaluated the pan-Akt inhibitor MK-2206 combination with standard therapy patients high-risk early-stage cancer.I-SPY 2 multicenter, phase II, open-label, adaptively randomized neoadjuvant platform trial that screens experimental therapies efficiently identifies potential predictive biomarker signatures. Patients are categorized by human epidermal...
<h3>Importance</h3> Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast trials. <h3>Objective</h3> To compare RCB between randomized control and investigational treatments within subtypes explore relationship with survival. <h3>Design, Setting, Participants</h3> The I-SPY2 is a multicenter, platform adaptive, clinical trial US that compares, by subtype, agents combination chemotherapy vs alone adult women stage 2/3 at high risk early...
The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.
Abstract The many improvements in breast cancer therapy recent years have so lowered rates of recurrence that it is now difficult or impossible to conduct adequately powered adjuvant clinical trials. Given the new drugs and potential synergistic combinations, neoadjuvant approach has been used test benefit drug combinations trials primary cancer. A FDA-led meta-analysis showed pathologic complete response (pCR) predicts disease-free survival (DFS) within patients who specific subtypes. This...
Abstract Background: I-SPY 2 is a multicenter, phase screening trial using adaptive randomization within biomarker subtypes to evaluate series of novel agents/combinations when added standard neoadjuvant therapy (paclitaxel q wk x 12, doxorubicin & cyclophosphamide 2-3 4, T/AC) vs. T/AC (control arm) for women with high-risk stage II/III breast cancer. The primary endpoint pathologic complete response (pCR) at surgery. Our goal identify/graduate regimens that have ≥85% Bayesian...
Abstract Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy triple negative signature. However, not all patients achieved pathologic complete response and some HR+HER2− responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1 ness, CIN70 expression signatures; PARP1 protein) performed on 116 HER2− (VC: 72...
Abstract HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two combinations neoadjuvant I-SPY2 phase 2 adaptive platform trial for cancer at high risk recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2 + cancer, adaptively randomized to T-DM1/P, THP, or a common control arm paclitaxel/trastuzumab (TH), followed by...
Abstract Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis proliferation. Trebananib was combined paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. Patients Methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients high-risk, early-stage to one of several experimental therapies or control based on receptor subtypes as defined by hormone (HR) HER2 status MammaPrint...
Abstract HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination standard chemotherapy patients high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling stage II-III cancer tumors 2.5 cm or larger on basis of hormone receptors (HR), HER2 Mammaprint status....
Abstract GBM AGILE (NCT03970447;https://www.gcaresearch.org/research/gbm-agile) is a phase 3 Bayesian adaptive platform trial that efficiently tests multiple arms against common control, with 6 included to date. Primary endpoint overall survival (OS). Stage 1 experimental are adaptively randomized other arms. Demonstrated efficacy in stage leads fixed randomization 2. Stages and 2 combined for registration. Control fixed. Regorafenib, multikinase-inhibitor, entered into as the first arm...
524 Background: A key node of growth and survival signaling pathways is the Akt serine/threonine kinase that activates mTOR downstream effectors. I-SPY 2 a randomized neoadjuvant trial to test agents combinations added standard chemotherapy. Pathological complete response (pCR) defined as absence invasive cancer in breast nodes primary endpoint. We report efficacy results for allosteric inhibitor MK-2206. Methods: Women with ≥2.5 cm on exam or ≥2 imaging were adaptively 12 weekly paclitaxel...