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

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

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.

引用

页数：11

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