دورية أكاديمية
Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.
| العنوان: | Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery. |
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| المؤلفون: | Albain KS; Loyola University Chicago Stritch School of Medicine, Maywood, Illinois., Yau C; University of California San Francisco, San Francisco, California., Petricoin EF; George Mason University, Fairfax, Virginia., Wolf DM; University of California San Francisco, San Francisco, California., Lang JE; Cleveland Clinic, Cleveland, Ohio., Chien AJ; University of California San Francisco, San Francisco, California., Haddad T; Mayo Clinic Rochester, Rochester, Minnesota., Forero-Torres A; University of Alabama at Birmingham, Birmingham, Alabama., Wallace AM; University of California San Diego, La Jolla, California., Kaplan H; Swedish Cancer Institute, Seattle, Washington., Pusztai L; Yale University, New Haven, Connecticut., Euhus D; Johns Hopkins University, Baltimore, Maryland., Nanda R; University of Chicago, Chicago, Illinois., Elias AD; University of Colorado Denver, Aurora, Colorado., Clark AS; University of Pennsylvania, Philadelphia, Pennsylvania., Godellas C; Loyola University Chicago Stritch School of Medicine, Maywood, Illinois., Boughey JC; Mayo Clinic Rochester, Rochester, Minnesota., Isaacs C; Georgetown University, Washington, District of Columbia., Tripathy D; University of Texas MD Anderson Cancer Center, Houston, Texas., Lu J; University of Southern California, Los Angeles, California., Yung RL; University of Washington, Seattle, Washington., Gallagher RI; George Mason University, Fairfax, Virginia., Wulfkuhle JD; George Mason University, Fairfax, Virginia., Brown-Swigart L; University of California San Francisco, San Francisco, California., Krings G; University of California San Francisco, San Francisco, California., Chen YY; University of California San Francisco, San Francisco, California., Potter DA; University of Minnesota, Minneapolis, Minnesota., Stringer-Reasor E; University of Alabama at Birmingham, Birmingham, Alabama., Blair S; University of California San Diego, La Jolla, California., Asare SM; Quantum Leap Healthcare Collaborative, San Francisco, California., Wilson A; Quantum Leap Healthcare Collaborative, San Francisco, California., Hirst GL; University of California San Francisco, San Francisco, California., Singhrao R; University of California San Francisco, San Francisco, California., Buxton M; University of California San Francisco, San Francisco, California., Clennell JL; University of California San Francisco, San Francisco, California., Sanil A; Berry Consultants, LLC, Houston, Texas., Berry S; Berry Consultants, LLC, Houston, Texas., Asare AL; Quantum Leap Healthcare Collaborative, San Francisco, California., Matthews JB; University of California San Francisco, San Francisco, California., DeMichele AM; University of Pennsylvania, Philadelphia, Pennsylvania., Hylton NM; University of California San Francisco, San Francisco, California., Melisko M; University of California San Francisco, San Francisco, California., Perlmutter J; Gemini Group, Ann Arbor, Michigan., Rugo HS; University of California San Francisco, San Francisco, California., Symmans WF; University of Texas MD Anderson Cancer Center, Houston, Texas., Van't Veer LJ; University of California San Francisco, San Francisco, California., Yee D; University of Minnesota, Minneapolis, Minnesota., Berry DA; Berry Consultants, LLC, Houston, Texas., Esserman LJ; University of California San Francisco, San Francisco, California. |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Feb 16; Vol. 30 (4), pp. 729-740. |
| نوع المنشور: | Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Breast Neoplasms*/drug therapy , Breast Neoplasms*/genetics , Breast Neoplasms*/pathology , Recombinant Fusion Proteins*, Female ; Humans ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Bayes Theorem ; Neoadjuvant Therapy ; Paclitaxel/adverse effects ; Receptor, ErbB-2/metabolism ; Receptor, TIE-2 ; Trastuzumab/adverse effects |
| مستخلص: | Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. Patients and Methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy "graduates" if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. Results: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%-99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. Conclusions: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority >90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted. (©2023 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | P01 CA210961 United States CA NCI NIH HHS |
| المشرفين على المادة: | P88XT4IS4D (Paclitaxel) EC 2.7.10.1 (Receptor, ErbB-2) EC 2.7.10.1 (Receptor, TIE-2) 0 (Recombinant Fusion Proteins) P188ANX8CK (Trastuzumab) X8Y5U6NC7E (trebananib) |
| تواريخ الأحداث: | Date Created: 20231218 Date Completed: 20240219 Latest Revision: 20240817 |
| رمز التحديث: | 20240817 |
| مُعرف محوري في PubMed: | PMC10956403 |
| DOI: | 10.1158/1078-0432.CCR-22-2256 |
| PMID: | 38109213 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1557-3265 |
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| DOI: | 10.1158/1078-0432.CCR-22-2256 |