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Durvalumab With Olaparib and Paclitaxel for High-Risk HER2-Negative Stage II/III Breast Cancer: Results From the Adaptively Randomized I-SPY2 Platform Trial

41 Pages Posted: 19 Dec 2020 Publication Status: Review Complete

See all articles by Lajos Pusztai

Lajos Pusztai

Yale University

Christina Yau

University of California, San Francisco (UCSF)

Denise M. Wolf

University of California, San Francisco (UCSF)

Hyo S. Han

Moffitt Cancer Center

Lili Du

University of Texas at Houston - MD Anderson Cancer Center

Anne M. Wallace

University of California, San Diego (UCSD)

Erica Stringer-Reasor

University of Alabama at Birmingham

Judy C. Boughey

Mayo Clinic

A. Jo Chien

University of California, San Francisco (UCSF)

Anthony D. Elias

University of Colorado

Heather Beckwith

The University of Minnesota

Rita Nanda

University of Chicago

Kathy S. Albain

Loyola University of Chicago - Stritch School of Medicine

Amy S. Clark

University of Pennsylvania

Kathleen Kemmer

Oregon Health and Science University

Kevin M. Kalinsky

Columbia University

Claudine Isaacs

Georgetown University

Alexandra Thomas

Wake Forest University

Rebecca Shatsky

University of California, San Francisco (UCSF)

Teresa L. Helsten

University of California, San Francisco (UCSF)

Andres Forero-Torres

University of Alabama at Birmingham

Minetta C. Liu

Mayo Clinic

Lamorna Brown-Swigart

University of California, San Francisco (UCSF)

Emmanuel F. Petricoin

George Mason University

Julia D. Wulfkuhle

George Mason University

Smita M. Asare

Quantum Leap Healthcare Collaborative

Amy Wilson

Quantum Leap Healthcare Collaborative

Ruby Singhrao

University of California, San Francisco (UCSF)

Laura Sit

University of California, San Francisco (UCSF)

Gillian L. Hirst

University of California, San Francisco (UCSF)

Scott Berry

Berry Consultants, LLC

Ashish Sanil

Berry Consultants, LLC

Adam L. Asare

Quantum Leap Healthcare Collaborative

Jeffrey B. Matthews

University of California, San Francisco (UCSF)

Jane Perlmutter

Gemini Group

Michele Melisko

University of California, San Francisco (UCSF)

Hope S. Rugo

University of California, San Francisco (UCSF)

Richard B. Schwab

University of California, San Diego (UCSD)

W. Fraser Symmans

University of Texas at Houston - MD Anderson Cancer Center

Doug Yee

The University of Minnesota

Laura van't Veer

University of California, San Francisco (UCSF)

Nola M. Hylton

University of California, San Francisco (UCSF)

Angela M. DeMichele

University of Pennsylvania

Donald A. Berry

Berry Consultants, LLC

Laura J. Esserman

University of California, San Francisco (UCSF)

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Abstract

The combination of PD-L1-inhibitor durvalumab and PARP-inhibitor olaparib (DOP) in addition to standard neoadjuvant chemotherapy was investigated in the phase II I-SPY2 platform trial of stage II/III HER2-negative breast cancer. Seventy-three HER2-negative participants were randomized to DOP and 299 to standard of care control. DOP graduated in all subtypes, increasing pCR rates in all HER2-negative (22 to 37%), HR-positive/HER2-negative (14% to 28%), TNBC (27% to 47%). In HR-positive/HER2-negative cancers, pCR rate in MammaPrint ultra high (MP2) cases was considerably higher than MP1, 64% vs 22%. Overall,12.3% of patients in the experimental arm experienced immune-related grade 3 adverse events vs. 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 potential benefits over standard neoadjuvant therapy in HER2-negative early breast cancer, particularly in a highly sensitive subset of high-risk HR-positive/HER2-negative patients.

Keywords: Breast cancer; immunotherapy; DNA repair inhibitor; clinical trial

Suggested Citation

Pusztai, Lajos and Yau, Christina and Wolf, Denise M. and Han, Hyo S. and Du, Lili and Wallace, Anne M. and Stringer-Reasor, Erica and Boughey, Judy C. and Chien, A. Jo and Elias, Anthony D. and Beckwith, Heather and Nanda, Rita and Albain, Kathy S. and Clark, Amy S. and Kemmer, Kathleen and Kalinsky, Kevin M. and Isaacs, Claudine and Thomas, Alexandra and Shatsky, Rebecca and Helsten, Teresa L. and Forero-Torres, Andres and Liu, Minetta C. and Brown-Swigart, Lamorna and Petricoin, Emmanuel F. and Wulfkuhle, Julia D. and Asare, Smita M. and Wilson, Amy and Singhrao, Ruby and Sit, Laura and Hirst, Gillian L. and Berry, Scott and Sanil, Ashish and Asare, Adam L. and Matthews, Jeffrey B. and Perlmutter, Jane and Melisko, Michele and Rugo, Hope S. and Schwab, Richard B. and Symmans, W. Fraser and Yee, Doug and van't Veer, Laura and Hylton, Nola M. and DeMichele, Angela M. and Berry, Donald A. and Esserman, Laura J., Durvalumab With Olaparib and Paclitaxel for High-Risk HER2-Negative Stage II/III Breast Cancer: Results From the Adaptively Randomized I-SPY2 Platform Trial. Available at SSRN: https://ssrn.com/abstract=3751802 or http://dx.doi.org/10.2139/ssrn.3751802
This version of the paper has not been formally peer reviewed.

Lajos Pusztai (Contact Author)

Yale University ( email )

New Haven, CT
United States

Christina Yau

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Denise M. Wolf

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Hyo S. Han

Moffitt Cancer Center ( email )

12902 USF Magnolia Drive
Tampa, FL 33612
United States

Lili Du

University of Texas at Houston - MD Anderson Cancer Center ( email )

Houston, TX
United States

Anne M. Wallace

University of California, San Diego (UCSD) ( email )

9500 Gilman Drive
Mail Code 0502
La Jolla, CA 92093-0112
United States

Erica Stringer-Reasor

University of Alabama at Birmingham ( email )

Birmingham, AL 35294-4460
United States

Judy C. Boughey

Mayo Clinic ( email )

200 First Street SW
Rochester, MN (507) 284-2511 55905
United States

A. Jo Chien

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Anthony D. Elias

University of Colorado ( email )

1475 Lawrence St
Denver, CO 80238-3363
United States

Heather Beckwith

The University of Minnesota ( email )

MN
United States

Rita Nanda

University of Chicago ( email )

1101 East 58th Street
Chicago, IL 60637
United States

Kathy S. Albain

Loyola University of Chicago - Stritch School of Medicine ( email )

Maywood, IL 60153
United States

Amy S. Clark

University of Pennsylvania ( email )

Philadelphia, PA 19104
United States

Kathleen Kemmer

Oregon Health and Science University ( email )

3181 S.W. Sam Jackson Park Rd.
Portland, OR 97201
United States

Kevin M. Kalinsky

Columbia University ( email )

3022 Broadway
New York, NY 10027
United States

Claudine Isaacs

Georgetown University ( email )

Washington, DC 20057
United States

Alexandra Thomas

Wake Forest University

2601 Wake Forest Road
Winston-Salem, NC 27109
United States

Rebecca Shatsky

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Teresa L. Helsten

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Andres Forero-Torres

University of Alabama at Birmingham ( email )

Birmingham, AL 35294-4460
United States

Minetta C. Liu

Mayo Clinic ( email )

200 First Street SW
Rochester, MN (507) 284-2511 55905
United States

Lamorna Brown-Swigart

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Emmanuel F. Petricoin

George Mason University ( email )

4400 University Drive
Fairfax, VA 22030
United States

Julia D. Wulfkuhle

George Mason University ( email )

4400 University Drive
Fairfax, VA 22030
United States

Smita M. Asare

Quantum Leap Healthcare Collaborative ( email )

Amy Wilson

Quantum Leap Healthcare Collaborative

Ruby Singhrao

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Laura Sit

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Gillian L. Hirst

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Scott Berry

Berry Consultants, LLC

Austin, TX
United States

Ashish Sanil

Berry Consultants, LLC ( email )

Austin, TX
United States

Adam L. Asare

Quantum Leap Healthcare Collaborative ( email )

Jeffrey B. Matthews

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Jane Perlmutter

Gemini Group ( email )

Michele Melisko

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Hope S. Rugo

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Richard B. Schwab

University of California, San Diego (UCSD) ( email )

9500 Gilman Drive
Mail Code 0502
La Jolla, CA 92093-0112
United States

W. Fraser Symmans

University of Texas at Houston - MD Anderson Cancer Center ( email )

Houston, TX
United States

Doug Yee

The University of Minnesota ( email )

MN
United States

Laura Van't Veer

University of California, San Francisco (UCSF) ( email )

CA
United States

Nola M. Hylton

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Angela M. DeMichele

University of Pennsylvania ( email )

Philadelphia, PA 19104
United States

Donald A. Berry

Berry Consultants, LLC ( email )

Austin, TX
United States

Laura J. Esserman

University of California, San Francisco (UCSF) ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

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