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

Authors

• M.A. Hennessy, University College Cork, Cork, Ireland
• C. Gatsonis, Brown University School of Public Health, Providence, RI
• H. Jacene, Dana-Farber/Brigham Cancer Center, Boston, MA
• R.M. Connolly, University College Cork, Cork, Ireland
• B.L. Burnette, Saint Vincent Hospital Cancer Center Green Bay, Green Bay, WI
• E.M. Stringer-Reasor, University of Alabama at Birmingham, Birmingham, AL
• J. Romanoff, Brown University School of Public Health, Providence, RI
• A. Taurone, Brown University School of Public Health, Providence, RI
• C.C. O’Sullivan, Mayo Clinic, Rochester, MN
• H.T. Le-Petross, University of Texas MD Anderson Cancer Center, Houston, TX
• V. Stearns, John Hopkins University, Baltimore, MD
• A.M. Fowler, University of Wisconsin Carbone Cancer Center, Madison, WI
• Shou-Ching Tang, LSU Health Sciences Center - New OrleansFollow
• K.A. Sepulveda, Baylor College of Medicine, Houston, TX
• A.M. DeMichele, University of Pennsylvania, Philadelphia, PA
• D.A. Mankoff, University of Pennsylvania, Philadelphia, PA
• A.C. Wolff, John Hopkins University, Baltimore, MD

Document Type

Article

Publication Date

10-5-2025

Publication Title

Future Oncology

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.

First Page

3377

Last Page

3384

PubMed ID

41047708

Volume

21

Issue

26

Rights

© 2026 Taylor & Francis

Recommended Citation

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, Shou-Ching; Sepulveda, K.A.; DeMichele, A.M.; Mankoff, D.A.; and Wolff, A.C., "EA1211: interim FDG-PET/CT for predicting response of HER2-positive breast cancer to neoadjuvant therapy (DIRECT trial)" (2025). School of Medicine Faculty Publications. 4761.
https://digitalscholar.lsuhsc.edu/som_facpubs/4761
10.1080/14796694.2025.2567840