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. van ‘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; Angela M. DeMichele

doi:10.1038/s41467-021-26019-y

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. van ‘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 YungDebu 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, Angela M. DeMichele

Gastroenterologic and General Surgery

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	6428
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-26019-y
State	Published - Dec 1 2021

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

Access to Document

10.1038/s41467-021-26019-y

Cite this

Clark, A. S., Yau, C., Wolf, D. M., Petricoin, E. F., van ‘t Veer, L. J., Yee, D., Moulder, S. L., Wallace, A. M., Chien, A. J., Isaacs, C., Boughey, J. C., Albain, K. S., Kemmer, K., Haley, B. B., Han, H. S., Forero-Torres, A., Elias, A., Lang, J. E., Ellis, E. D., ... DeMichele, A. M. (2021). Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2⁺ breast cancer in the adaptively randomized I-SPY2 trial. Nature communications, 12(1), Article 6428. https://doi.org/10.1038/s41467-021-26019-y

Clark, AS, Yau, C, Wolf, DM, Petricoin, EF, van ‘t Veer, LJ, Yee, D, Moulder, SL, Wallace, AM, Chien, AJ, Isaacs, C, Boughey, JC, Albain, KS, Kemmer, K, Haley, BB, Han, HS, Forero-Torres, A, Elias, A, Lang, JE, Ellis, ED, Yung, R, Tripathy, D, Nanda, R, Wulfkuhle, JD, Brown-Swigart, L, Gallagher, RI, Helsten, T, Roesch, E, Ewing, CA, Alvarado, M, Crane, EP, Buxton, M, Clennell, JL, Paoloni, M, Asare, SM, Wilson, A, Hirst, GL, Singhrao, R, Steeg, K, Asare, A, Matthews, JB, Berry, S, Sanil, A, Melisko, M, Perlmutter, J, Rugo, HS, Schwab, RB, Symmans, WF, Hylton, NM, Berry, DA, Esserman, LJ & DeMichele, AM 2021, 'Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2⁺ breast cancer in the adaptively randomized I-SPY2 trial', Nature communications, vol. 12, no. 1, 6428. https://doi.org/10.1038/s41467-021-26019-y

@article{42a463efcd1c44d0b44fbd93aac9c549,

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

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 {\textquoteleft}graduate{\textquoteright} 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.",

author = "Clark, {Amy S.} and Christina Yau and Wolf, {Denise M.} and Petricoin, {Emanuel F.} and {van {\textquoteleft}t Veer}, {Laura J.} and Douglas Yee and Moulder, {Stacy L.} and Wallace, {Anne M.} and Chien, {A. Jo} and Claudine Isaacs and Boughey, {Judy C.} and Albain, {Kathy S.} and Kathleen Kemmer and Haley, {Barbara B.} and Han, {Hyo S.} and Andres Forero-Torres and Anthony Elias and Lang, {Julie E.} and Ellis, {Erin D.} and Rachel Yung and Debu Tripathy and Rita Nanda and Wulfkuhle, {Julia D.} and Lamorna Brown-Swigart and Gallagher, {Rosa I.} and Teresa Helsten and Erin Roesch and Ewing, {Cheryl A.} and Michael Alvarado and Crane, {Erin P.} and Meredith Buxton and Clennell, {Julia L.} and Melissa Paoloni and Asare, {Smita M.} and Amy Wilson and Hirst, {Gillian L.} and Ruby Singhrao and Katherine Steeg and Adam Asare and Matthews, {Jeffrey B.} and Scott Berry and Ashish Sanil and Michelle Melisko and Jane Perlmutter and Rugo, {Hope S.} and Schwab, {Richard B.} and Symmans, {W. Fraser} and Hylton, {Nola M.} and Berry, {Donald A.} and Esserman, {Laura J.} and DeMichele, {Angela M.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-021-26019-y",

language = "English (US)",

volume = "12",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial

AU - Clark, Amy S.

AU - Yau, Christina

AU - Wolf, Denise M.

AU - Petricoin, Emanuel F.

AU - van ‘t Veer, Laura J.

AU - Yee, Douglas

AU - Moulder, Stacy L.

AU - Wallace, Anne M.

AU - Chien, A. Jo

AU - Isaacs, Claudine

AU - Boughey, Judy C.

AU - Albain, Kathy S.

AU - Kemmer, Kathleen

AU - Haley, Barbara B.

AU - Han, Hyo S.

AU - Forero-Torres, Andres

AU - Elias, Anthony

AU - Lang, Julie E.

AU - Ellis, Erin D.

AU - Yung, Rachel

AU - Tripathy, Debu

AU - Nanda, Rita

AU - Wulfkuhle, Julia D.

AU - Brown-Swigart, Lamorna

AU - Gallagher, Rosa I.

AU - Helsten, Teresa

AU - Roesch, Erin

AU - Ewing, Cheryl A.

AU - Alvarado, Michael

AU - Crane, Erin P.

AU - Buxton, Meredith

AU - Clennell, Julia L.

AU - Paoloni, Melissa

AU - Asare, Smita M.

AU - Wilson, Amy

AU - Hirst, Gillian L.

AU - Singhrao, Ruby

AU - Steeg, Katherine

AU - Asare, Adam

AU - Matthews, Jeffrey B.

AU - Berry, Scott

AU - Sanil, Ashish

AU - Melisko, Michelle

AU - Perlmutter, Jane

AU - Rugo, Hope S.

AU - Schwab, Richard B.

AU - Symmans, W. Fraser

AU - Hylton, Nola M.

AU - Berry, Donald A.

AU - Esserman, Laura J.

AU - DeMichele, Angela M.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85118560823&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85118560823&partnerID=8YFLogxK

U2 - 10.1038/s41467-021-26019-y

DO - 10.1038/s41467-021-26019-y

M3 - Article

C2 - 34741023

AN - SCOPUS:85118560823

SN - 2041-1723

VL - 12

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 6428

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this