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

被引:57
作者
Clark, Amy S. [1 ]
Yau, Christina [2 ]
Wolf, Denise M. [2 ]
Petricoin, Emanuel F. [3 ]
Veer, Laura J. van't [2 ]
Yee, Douglas [4 ]
Moulder, Stacy L. [5 ]
Wallace, Anne M. [6 ]
Chien, A. Jo [2 ]
Isaacs, Claudine [7 ]
Boughey, Judy C. [8 ]
Albain, Kathy S. [9 ]
Kemmer, Kathleen [10 ]
Haley, Barbara B. [11 ]
Han, Hyo S. [12 ]
Forero-Torres, Andres [13 ]
Elias, Anthony [14 ]
Lang, Julie E. [15 ]
Ellis, Erin D. [16 ]
Yung, Rachel [17 ]
Tripathy, Debu [5 ]
Nanda, Rita [18 ]
Wulfkuhle, Julia D. [5 ]
Brown-Swigart, Lamorna [2 ]
Gallagher, Rosa, I [5 ]
Helsten, Teresa [6 ]
Roesch, Erin [6 ]
Ewing, Cheryl A. [2 ]
Alvarado, Michael [2 ]
Crane, Erin P. [7 ]
Buxton, Meredith [19 ]
Clennell, Julia L. [19 ]
Paoloni, Melissa [19 ]
Asare, Smita M. [2 ]
Wilson, Amy [2 ]
Hirst, Gillian L. [2 ]
Singhrao, Ruby [2 ]
Steeg, Katherine [2 ]
Asare, Adam [2 ]
Matthews, Jeffrey B. [2 ]
Berry, Scott [19 ]
Sanil, Ashish [19 ]
Melisko, Michelle [2 ]
Perlmutter, Jane [20 ]
Rugo, Hope S. [2 ]
Schwab, Richard B. [6 ]
Symmans, W. Fraser [5 ]
Hylton, Nola M. [2 ]
Berry, Donald A. [19 ]
Esserman, Laura J. [2 ]
机构
[1] Univ Penn, Philadelphia, PA 19104 USA
[2] Univ Calif San Francisco, San Francisco, CA 94143 USA
[3] George Mason Univ, Fairfax, VA 22030 USA
[4] Univ Minnesota, Minneapolis, MN USA
[5] MD Anderson Canc Ctr, Houston, TX USA
[6] Univ Calif San Diego, San Diego, CA 92103 USA
[7] Georgetown Univ, Washington, DC USA
[8] Mayo Clin, Rochester, MN USA
[9] Loyola Univ, Chicago, IL USA
[10] Oregon Hlth & Sci Univ, Portland, OR 97201 USA
[11] Univ Texas Southwestern, Dallas, TX USA
[12] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA
[13] Univ Alabama Birmingham, Birmingham, AL USA
[14] Univ Colorado Denver, Aurora, CO USA
[15] Univ Southern Calif, Los Angeles, CA 90007 USA
[16] Swedish Canc Inst, Seattle, WA USA
[17] Univ Washington, Seattle, WA 98195 USA
[18] Univ Chicago, Chicago, IL 60637 USA
[19] Berry Consultants LLC, Houston, TX USA
[20] Gemini Grp, Ann Arbor, MI USA
基金
美国国家卫生研究院;
关键词
PHASE-III; PLUS TRASTUZUMAB; PERTUZUMAB; DOCETAXEL; SAFETY;
D O I
10.1038/s41467-021-26019-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
HER2-targeted therapy improves patient's outcome in early breast cancer. Here, the authors present the efficacy and biomarker analysis of two HER2-targeted combinations (ado-trastuzumab emtansine plus pertuzumab and paclitaxel, trastuzumab and pertuzumab) in the context of the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence. 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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页数:11
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