EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)

Maeve A. Hennessy; Constantine Gatsonis; Heather Jacene; Roisin M. Connolly; Brian L. Burnette; Erica M. Stringer-Reasor; Justin Romanoff; Alexander Taurone; Ciara C. O’Sullivan; Huong T. Le-Petross; Vered Stearns; Amy M. Fowler; Shou Ching Tang; Karla A. Sepulveda; Angela M. DeMichele; David A. Mankoff; Antonio C. Wolff

doi:10.1080/14796694.2025.2567840

EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)

Maeve A. Hennessy
, Constantine Gatsonis
, Heather Jacene
, Roisin M. Connolly
, Brian L. Burnette
, Erica M. Stringer-Reasor
, Justin Romanoff
, Alexander Taurone
, Ciara C. O’Sullivan
, Huong T. Le-Petross
, Vered Stearns
, Amy M. Fowler
, Shou Ching Tang
, Karla A. Sepulveda
, Angela M. DeMichele
, David A. Mankoff
, Antonio C. Wolff

School of Medicine

Brown University
Dana-Farber Cancer Institute
St. Vincent Hospital, Green Bay
University of Alabama at Birmingham
Mayo Clinic Rochester, MN
University of Texas MD Anderson Cancer Center
Johns Hopkins University
University of Wisconsin-Madison
Louisiana State University Health Sciences Center
Baylor College of Medicine
University of Pennsylvania

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

Abstract

Recent studies indicate that early changes on 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) predict response to human epidermal growth factor receptor 2 (HER2)-directed therapy. EA1211/DIRECT is a multicenter, single-arm, primary imaging phase 2 study enrolling patients with stage II/III HER2-positive breast cancer receiving pertuzumab-based neoadjuvant therapy followed by surgery. The trial aims to validate FDG-PET/CT as a neoadjuvant interim (niFDG-PET/CT) imaging integral biomarker in patients treated with standard HER2-directed regimens. The primary objective is to estimate the negative predictive value of niFDG-PET/CT for pathologic complete response using delta maximum standardized uptake value corrected for lean body mass day 15 (ΔSULmaxD15) of the primary breast cancer at a threshold of 40%. If EA1211/DIRECT meets its objectives, the results will be used to design clinical utility studies for this noninvasive imaging biomarker, hoping to change practice toward a response-guided approach, ensuring patients receive treatment tailored to their tumor biology and individual response. Clinical trial registration: NCT05710328.

Original language	English
Journal	Future Oncology
DOIs	https://doi.org/10.1080/14796694.2025.2567840
Publication status	Accepted/In press - 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

clinical trials
FDG-PET/CT
HER2-positive breast cancer
imaging biomarkers
neoadjuvant
precision oncology

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10.1080/14796694.2025.2567840

Cite this

Hennessy, M. A., Gatsonis, C., Jacene, H., Connolly, R. M., Burnette, B. L., Stringer-Reasor, E. M., Romanoff, J., Taurone, A., O’Sullivan, C. C., Le-Petross, H. T., Stearns, V., Fowler, A. M., Tang, S. C., Sepulveda, K. A., DeMichele, A. M., Mankoff, D. A., & Wolff, A. C. (Accepted/In press). EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial). Future Oncology. https://doi.org/10.1080/14796694.2025.2567840

@article{18ce4c569e4e4aca8b42821515aab447,

title = "EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)",

abstract = "Recent studies indicate that early changes on 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) predict response to human epidermal growth factor receptor 2 (HER2)-directed therapy. EA1211/DIRECT is a multicenter, single-arm, primary imaging phase 2 study enrolling patients with stage II/III HER2-positive breast cancer receiving pertuzumab-based neoadjuvant therapy followed by surgery. The trial aims to validate FDG-PET/CT as a neoadjuvant interim (niFDG-PET/CT) imaging integral biomarker in patients treated with standard HER2-directed regimens. The primary objective is to estimate the negative predictive value of niFDG-PET/CT for pathologic complete response using delta maximum standardized uptake value corrected for lean body mass day 15 (ΔSULmaxD15) of the primary breast cancer at a threshold of 40\%. If EA1211/DIRECT meets its objectives, the results will be used to design clinical utility studies for this noninvasive imaging biomarker, hoping to change practice toward a response-guided approach, ensuring patients receive treatment tailored to their tumor biology and individual response. Clinical trial registration: NCT05710328.",

keywords = "clinical trials, FDG-PET/CT, HER2-positive breast cancer, imaging biomarkers, neoadjuvant, precision oncology",

author = "Hennessy, \{Maeve A.\} and Constantine Gatsonis and Heather Jacene and Connolly, \{Roisin M.\} and Burnette, \{Brian L.\} and Stringer-Reasor, \{Erica M.\} and Justin Romanoff and Alexander Taurone and O{\textquoteright}Sullivan, \{Ciara C.\} and Le-Petross, \{Huong T.\} and Vered Stearns and Fowler, \{Amy M.\} and Tang, \{Shou Ching\} and Sepulveda, \{Karla A.\} and DeMichele, \{Angela M.\} and Mankoff, \{David A.\} and Wolff, \{Antonio C.\}",

note = "Publisher Copyright: {\textcopyright} 2025 Informa UK Limited, trading as Taylor \& Francis Group.",

year = "2025",

doi = "10.1080/14796694.2025.2567840",

language = "English",

journal = "Future Oncology",

issn = "1479-6694",

publisher = "Taylor and Francis Ltd.",

}

Hennessy, MA, Gatsonis, C, Jacene, H, Connolly, RM, Burnette, BL, Stringer-Reasor, EM, Romanoff, J, Taurone, A, O’Sullivan, CC, Le-Petross, HT, Stearns, V, Fowler, AM, Tang, SC, Sepulveda, KA, DeMichele, AM, Mankoff, DA & Wolff, AC 2025, 'EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)', Future Oncology. https://doi.org/10.1080/14796694.2025.2567840

TY - JOUR

T1 - EA1211

T2 - interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)

AU - Hennessy, Maeve A.

AU - Gatsonis, Constantine

AU - Jacene, Heather

AU - Connolly, Roisin M.

AU - Burnette, Brian L.

AU - Stringer-Reasor, Erica M.

AU - Romanoff, Justin

AU - Taurone, Alexander

AU - O’Sullivan, Ciara C.

AU - Le-Petross, Huong T.

AU - Stearns, Vered

AU - Fowler, Amy M.

AU - Tang, Shou Ching

AU - Sepulveda, Karla A.

AU - DeMichele, Angela M.

AU - Mankoff, David A.

AU - Wolff, Antonio C.

PY - 2025

Y1 - 2025

N2 - Recent studies indicate that early changes on 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) predict response to human epidermal growth factor receptor 2 (HER2)-directed therapy. EA1211/DIRECT is a multicenter, single-arm, primary imaging phase 2 study enrolling patients with stage II/III HER2-positive breast cancer receiving pertuzumab-based neoadjuvant therapy followed by surgery. The trial aims to validate FDG-PET/CT as a neoadjuvant interim (niFDG-PET/CT) imaging integral biomarker in patients treated with standard HER2-directed regimens. The primary objective is to estimate the negative predictive value of niFDG-PET/CT for pathologic complete response using delta maximum standardized uptake value corrected for lean body mass day 15 (ΔSULmaxD15) of the primary breast cancer at a threshold of 40%. If EA1211/DIRECT meets its objectives, the results will be used to design clinical utility studies for this noninvasive imaging biomarker, hoping to change practice toward a response-guided approach, ensuring patients receive treatment tailored to their tumor biology and individual response. Clinical trial registration: NCT05710328.

AB - Recent studies indicate that early changes on 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT) predict response to human epidermal growth factor receptor 2 (HER2)-directed therapy. EA1211/DIRECT is a multicenter, single-arm, primary imaging phase 2 study enrolling patients with stage II/III HER2-positive breast cancer receiving pertuzumab-based neoadjuvant therapy followed by surgery. The trial aims to validate FDG-PET/CT as a neoadjuvant interim (niFDG-PET/CT) imaging integral biomarker in patients treated with standard HER2-directed regimens. The primary objective is to estimate the negative predictive value of niFDG-PET/CT for pathologic complete response using delta maximum standardized uptake value corrected for lean body mass day 15 (ΔSULmaxD15) of the primary breast cancer at a threshold of 40%. If EA1211/DIRECT meets its objectives, the results will be used to design clinical utility studies for this noninvasive imaging biomarker, hoping to change practice toward a response-guided approach, ensuring patients receive treatment tailored to their tumor biology and individual response. Clinical trial registration: NCT05710328.

KW - clinical trials

KW - FDG-PET/CT

KW - HER2-positive breast cancer

KW - imaging biomarkers

KW - neoadjuvant

KW - precision oncology

UR - https://www.scopus.com/pages/publications/105018625783

U2 - 10.1080/14796694.2025.2567840

DO - 10.1080/14796694.2025.2567840

M3 - Article

C2 - 41047708

AN - SCOPUS:105018625783

SN - 1479-6694

JO - Future Oncology

JF - Future Oncology

ER -

EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)

Abstract

UN SDGs

Keywords

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