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Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial

Author

Listed:
  • Amy S. Clark

    (University of Pennsylvania)

  • Christina Yau

    (University of California San Francisco)

  • Denise M. Wolf

    (University of California San Francisco)

  • Emanuel F. Petricoin

    (George Mason University)

  • Laura J. ‘t Veer

    (University of California San Francisco)

  • Douglas Yee

    (University of Minnesota)

  • Stacy L. Moulder

    (MD Anderson Cancer Center)

  • Anne M. Wallace

    (University of California San Diego)

  • A. Jo Chien

    (University of California San Francisco)

  • Claudine Isaacs

    (Georgetown University)

  • Judy C. Boughey

    (Mayo Clinic)

  • Kathy S. Albain

    (Loyola University)

  • Kathleen Kemmer

    (Oregon Health & Science University)

  • Barbara B. Haley

    (University of Texas Southwestern)

  • Hyo S. Han

    (Moffitt Cancer Center)

  • Andres Forero-Torres

    (University of Alabama Birmingham)

  • Anthony Elias

    (University of Colorado Denver)

  • Julie E. Lang

    (University of Southern California)

  • Erin D. Ellis

    (Swedish Cancer Institute)

  • Rachel Yung

    (University of Washington)

  • Debu Tripathy

    (MD Anderson Cancer Center)

  • Rita Nanda

    (University of Chicago)

  • Julia D. Wulfkuhle

    (MD Anderson Cancer Center)

  • Lamorna Brown-Swigart

    (University of California San Francisco)

  • Rosa I. Gallagher

    (MD Anderson Cancer Center)

  • Teresa Helsten

    (University of California San Diego)

  • Erin Roesch

    (University of California San Diego)

  • Cheryl A. Ewing

    (University of California San Francisco)

  • Michael Alvarado

    (University of California San Francisco)

  • Erin P. Crane

    (Georgetown University)

  • Meredith Buxton

    (Berry Consultants, LLC)

  • Julia L. Clennell

    (Berry Consultants, LLC)

  • Melissa Paoloni

    (Berry Consultants, LLC)

  • Smita M. Asare

    (University of California San Francisco)

  • Amy Wilson

    (University of California San Francisco)

  • Gillian L. Hirst

    (University of California San Francisco)

  • Ruby Singhrao

    (University of California San Francisco)

  • Katherine Steeg

    (University of California San Francisco)

  • Adam Asare

    (University of California San Francisco)

  • Jeffrey B. Matthews

    (University of California San Francisco)

  • Scott Berry

    (Berry Consultants, LLC)

  • Ashish Sanil

    (Berry Consultants, LLC)

  • Michelle Melisko

    (University of California San Francisco)

  • Jane Perlmutter

    (Gemini Group)

  • Hope S. Rugo

    (University of California San Francisco)

  • Richard B. Schwab

    (University of California San Diego)

  • W. Fraser Symmans

    (MD Anderson Cancer Center)

  • Nola M. Hylton

    (University of California San Francisco)

  • Donald A. Berry

    (Berry Consultants, LLC)

  • Laura J. Esserman

    (University of California San Francisco)

  • Angela M. DeMichele

    (University of Pennsylvania)

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.

Suggested Citation

  • Amy S. Clark & Christina Yau & Denise M. Wolf & Emanuel F. Petricoin & Laura J. ‘t Veer & Douglas Yee & Stacy L. Moulder & Anne M. Wallace & A. Jo Chien & Claudine Isaacs & Judy C. Boughey & Kathy S. , 2021. "Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26019-y
    DOI: 10.1038/s41467-021-26019-y
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