Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2
washington; seattle; swedish cancer
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.
Women & Children
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; and DeMichele, Angela M, "Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2" (2021). Articles, Abstracts, and Reports. 5433.