Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial

被引：197

作者：

Pusztai, Lajos ^{[1
]}

Yau, Christina ^{[2
]}

Wolf, Denise M. ^{[3
]}

Han, Hyo S. ^{[4
]}

Du, Lili ^{[5
]}

Wallace, Anne M. ^{[6
]}

String-Reasor, Erica ^{[7
]}

Boughey, Judy C. ^{[8
]}

Chien, A. Jo ^{[2
]}

Elias, Anthony D. ^{[9
]}

Beckwith, Heather ^{[10
]}

Nanda, Rita ^{[11
]}

Albain, Kathy S. ^{[12
]}

Clark, Amy S. ^{[13
]}

Kemmer, Kathleen ^{[14
]}

Kalinsky, Kevin ^{[15
]}

Isaacs, Claudine ^{[16
]}

Thomas, Alexandra ^{[17
]}

Shatsky, Rebecca ^{[6
]}

Helsten, Theresa L. ^{[18
]}

Forero-Torres, Andres ^{[7
]}

Liu, Minetta C. ^{[8
]}

Brown-Swigart, Lamorna ^{[3
]}

Petricoin, Emmanuel F. ^{[19
]}

Wulfkuhle, Julia D. ^{[19
]}

Asare, Smita M. ^{[20
]}

Wilson, Amy ^{[20
]}

Singhrao, Ruby ^{[2
]}

Sit, Laura ^{[2
]}

Hirst, Gillian L. ^{[2
]}

Berry, Scott ^{[21
]}

Sanil, Ashish ^{[21
]}

Asare, Adam L. ^{[20
]}

Matthews, Jeffrey B. ^{[2
]}

Perlmutter, Jane ^{[22
]}

Melisko, Michelle ^{[2
]}

Rugo, Hope S. ^{[2
]}

Schwab, Richard B. ^{[18
]}

Symmans, W. Fraser ^{[5
]}

Yee, Doug ^{[10
]}

Van't Veer, Laura J. ^{[2
]}

Hylton, Nola M. ^{[2
]}

DeMichele, Angela M. ^{[13
]}

Berry, Donald A. ^{[21
]}

Esserman, Laura J. ^{[2
]}

机构：

[1] Yale Sch Med, Yale Canc Ctr, Breast Med Oncol, 333 Cedar Steet,POB 208032, New Haven, CT 06510 USA

[2] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

[4] H Lee Moffitt Canc Ctr & Res Inst, Med Oncol, Tampa, FL 33612 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[6] Univ Calif San Diego, Comprehens Breast Hlth Ctr, La Jolla, CA 92037 USA

[7] Univ Alabama Birmingham, Dept Hematol & Oncol, Birmingham, AL 35233 USA

[8] Mayo Clin, Dept Surg, Rochester, MN 55905 USA

[9] Univ Colorado, Dept Internal Med, Aurora, CO 80045 USA

[10] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA

[11] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[12] Loyola Univ, Stritch Sch Med, Hematol Oncol, Chicago, IL 60153 USA

[13] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA

[14] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA

[15] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA

[16] Georgetown Univ, Lombardi Comprehens Care Ctr, Washington, DC 20007 USA

[17] Wake Forest Univ, Med Oncol & Hematol, Winston Salem, NC 27157 USA

[18] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92037 USA

[19] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA

[20] Quantum Leap Healthcare Collaborat, San Francisco, CA 94118 USA

[21] Berry Consultants LLC, Austin, TX 78746 USA

[22] Gemini Grp, Ann Arbor, MI 48107 USA

来源：

CANCER CELL | 2021年 / 39卷 / 07期

基金：

美国国家卫生研究院;

关键词：

I-SPY; 2; THERAPY;

D O I：

10.1016/j.ccell.2021.05.009

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The combination of PD-L1 inhibitor durvalumab and PARP inhibitor olaparib added to standard paclitaxel neoadjuvant chemotherapy (durvalumab/olaparib/paclitaxel [DOP]) was investigated in the phase II I-SPY2 trial of stage II/III HER2-negative breast cancer. Seventy-three participants were randomized to DOP and 299 to standard of care (paclitaxel) control. DOP increased pathologic complete response (pCR) rates in all HER2-negative (20%-37%), hormone receptor (HR)-positive/HER2-negative (14%-28%), and triple-negative breast cancer (TNBC) (27%-47%). In HR-positive/HER2-negative cancers, MammaPrint ultra-high (MP2) cases benefited selectively from DOP(pCR 64% versus 22%), no benefit was seen in MP1 cancers (pCR9% versus 10%). Overall, 12.3% of patients in the DOP arm experienced immune-related grade 3 adverse events versus 1.3% in control. Gene expression signatures associated with immune response were positively associated with pCR in both arms, while a mast cell signature was associated with non-pCR. DOP has superior efficacy over standard neoadjuvant chemotherapy in HER2-negative breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.

引用

页码：989 / +

页数：15

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