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Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial.
Clark, Amy S; Yau, Christina; Wolf, Denise M; Petricoin, Emanuel F; van 't Veer, Laura J; Yee, Douglas; Moulder, Stacy L; Wallace, Anne M; Chien, A Jo; Isaacs, Claudine; Boughey, Judy C; Albain, Kathy S; Kemmer, Kathleen; Haley, Barbara B; Han, Hyo S; Forero-Torres, Andres; Elias, Anthony; Lang, Julie E; Ellis, Erin D; Yung, Rachel; Tripathy, Debu; Nanda, Rita; Wulfkuhle, Julia D; Brown-Swigart, Lamorna; Gallagher, Rosa I; Helsten, Teresa; Roesch, Erin; Ewing, Cheryl A; Alvarado, Michael; Crane, Erin P; Buxton, Meredith; Clennell, Julia L; Paoloni, Melissa; Asare, Smita M; Wilson, Amy; Hirst, Gillian L; Singhrao, Ruby; Steeg, Katherine; Asare, Adam; Matthews, Jeffrey B; Berry, Scott; Sanil, Ashish; Melisko, Michelle; Perlmutter, Jane; Rugo, Hope S; Schwab, Richard B; Symmans, W Fraser; Hylton, Nola M; Berry, Donald A; Esserman, Laura J.
Afiliação
  • Clark AS; University of Pennsylvania, Philadelphia, PA, USA. Amy.Clark@pennmedicine.upenn.edu.
  • Yau C; University of California San Francisco, San Francisco, CA, USA.
  • Wolf DM; University of California San Francisco, San Francisco, CA, USA.
  • Petricoin EF; George Mason University, Fairfax, VA, USA.
  • van 't Veer LJ; University of California San Francisco, San Francisco, CA, USA.
  • Yee D; University of Minnesota, Minneapolis, MN, USA.
  • Moulder SL; MD Anderson Cancer Center, Houston, TX, USA.
  • Wallace AM; University of California San Diego, San Diego, CA, USA.
  • Chien AJ; University of California San Francisco, San Francisco, CA, USA.
  • Isaacs C; Georgetown University, Washington, DC, USA.
  • Boughey JC; Mayo Clinic, Rochester, MN, USA.
  • Albain KS; Loyola University, Chicago, IL, USA.
  • Kemmer K; Oregon Health & Science University, Portland, OR, USA.
  • Haley BB; University of Texas Southwestern, Dallas, TX, USA.
  • Han HS; Moffitt Cancer Center, Tampa, FL, USA.
  • Forero-Torres A; University of Alabama Birmingham, Birmingham, AL, USA.
  • Elias A; University of Colorado Denver, Aurora, CO, USA.
  • Lang JE; University of Southern California, Los Angeles, CA, USA.
  • Ellis ED; Swedish Cancer Institute, Seattle, WA, USA.
  • Yung R; University of Washington, Seattle, WA, USA.
  • Tripathy D; MD Anderson Cancer Center, Houston, TX, USA.
  • Nanda R; University of Chicago, Chicago, IL, USA.
  • Wulfkuhle JD; MD Anderson Cancer Center, Houston, TX, USA.
  • Brown-Swigart L; University of California San Francisco, San Francisco, CA, USA.
  • Gallagher RI; MD Anderson Cancer Center, Houston, TX, USA.
  • Helsten T; University of California San Diego, San Diego, CA, USA.
  • Roesch E; University of California San Diego, San Diego, CA, USA.
  • Ewing CA; University of California San Francisco, San Francisco, CA, USA.
  • Alvarado M; University of California San Francisco, San Francisco, CA, USA.
  • Crane EP; Georgetown University, Washington, DC, USA.
  • Buxton M; Berry Consultants, LLC, Houston, TX, USA.
  • Clennell JL; Berry Consultants, LLC, Houston, TX, USA.
  • Paoloni M; Berry Consultants, LLC, Houston, TX, USA.
  • Asare SM; University of California San Francisco, San Francisco, CA, USA.
  • Wilson A; University of California San Francisco, San Francisco, CA, USA.
  • Hirst GL; University of California San Francisco, San Francisco, CA, USA.
  • Singhrao R; University of California San Francisco, San Francisco, CA, USA.
  • Steeg K; University of California San Francisco, San Francisco, CA, USA.
  • Asare A; University of California San Francisco, San Francisco, CA, USA.
  • Matthews JB; University of California San Francisco, San Francisco, CA, USA.
  • Berry S; Berry Consultants, LLC, Houston, TX, USA.
  • Sanil A; Berry Consultants, LLC, Houston, TX, USA.
  • Melisko M; University of California San Francisco, San Francisco, CA, USA.
  • Perlmutter J; Gemini Group, Ann Arbor, MI, USA.
  • Rugo HS; University of California San Francisco, San Francisco, CA, USA.
  • Schwab RB; University of California San Diego, San Diego, CA, USA.
  • Symmans WF; MD Anderson Cancer Center, Houston, TX, USA.
  • Hylton NM; University of California San Francisco, San Francisco, CA, USA.
  • Berry DA; Berry Consultants, LLC, Houston, TX, USA.
  • Esserman LJ; University of California San Francisco, San Francisco, CA, USA.
Nat Commun ; 12(1): 6428, 2021 11 05.
Article em En | MEDLINE | ID: mdl-34741023
ABSTRACT
HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+ breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms 'graduate' in all subtypes predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+ tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Terapia Neoadjuvante / Ado-Trastuzumab Emtansina Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Aged / Humans / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Terapia Neoadjuvante / Ado-Trastuzumab Emtansina Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Aged / Humans / Middle aged Idioma: En Ano de publicação: 2021 Tipo de documento: Article