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

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. Albain, Kathleen Kemmer, Barbara B. Haley, Hyo S. Han, Andres Forero-Torres, Anthony Elias, Julie E. Lang, Erin D. Ellis, Rachel Yung, Debu Tripathy, Rita Nanda, Julia D. Wulfkuhle, Lamorna Brown-Swigart, Rosa I. Gallagher, Teresa Helsten, Erin Roesch, Cheryl A. Ewing, Michael Alvarado, Erin P. Crane, Meredith Buxton, Julia L. Clennell, Melissa Paoloni, Smita M. Asare, Amy Wilson, Gillian L. Hirst, Ruby Singhrao, Katherine Steeg, Adam Asare, Jeffrey B. Matthews, Scott Berry, Ashish Sanil, Michelle Melisko, Jane Perlmutter, Hope S. Rugo, Richard B. Schwab, W. Fraser Symmans, Nola M. Hylton, Donald A. Berry, Laura J. Esserman and Angela M. DeMichele
Additional contact information
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

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26019-y

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