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Clinical Trial
. 2025 Nov;21(26):3377-3384.
doi: 10.1080/14796694.2025.2567840. Epub 2025 Oct 5.

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

Maeve A Hennessy  1 , Constantine Gatsonis  2 , Heather Jacene  3 , Roisin M Connolly  1   4 , Brian L Burnette  5 , Erica M Stringer-Reasor  6 , Justin Romanoff  2 , Alexander Taurone  2 , Ciara C O'Sullivan  7 , Huong T Le-Petross  8 , Vered Stearns  9 , Amy M Fowler  10 , Shou-Ching Tang  11 , Karla A Sepulveda  12 , Angela M DeMichele  13 , David A Mankoff  13 , Antonio C Wolff  9
Affiliations
Clinical Trial

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

Maeve A Hennessy et al. Future Oncol. 2025 Nov.

Abstract

NCT05710328.

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

Plain language summary

Early-stage HER2-positive breast cancer is a subset of breast cancer that is usually treated with a combination of chemotherapy and HER2-targeted therapy before surgery, with the aim of shrinking down the tumor to provide a cure. The standard treatment involves several different drugs and is often linked to side effects. We want to find a way to figure out early in the treatment course if the treatment is working well to make better decisions for patients. The EA1211/DIRECT trial is testing whether a special type of imaging test, called FDG-PET/CT, 2–3 weeks after starting standard cancer treatment will help predict how breast cancer will shrink or respond by the time of surgery. FDG is a radioactive sugar-based tracer that is given in a vein before PET/CT imaging, which helps doctors see areas with active cancer. PET and CT scans are imaging techniques that make detailed pictures of areas inside the body. EA1211/DIRECT aims to find out if FDG-PET/CT can be used to make more personalized decisions around treatment for patients with HER2-positive breast cancer. The use of FDG-PET/CT may help doctors decide if a patient needs more or less treatment before surgery to achieve the best outcome. Overall, this study looks at whether FDG-PET/CT is useful in predicting how well patients will respond to standard chemotherapy treatments.

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Conflict of interest statement

MH: Travel/conference support from MSD, Roche, AstraZeneca. Spouse employed by Abbvie.

HJ: Section Editor for American Journal of Radiology, Royalties from Cambridge Publishing, Consulting for Blue Earth Diagnostics, Spectrum Dynamics; Honoraria from Elsevier, intouchCONGRESS, Dana-Farber, Monrol, Nanets/ITM; Support for meetings/travel from SNMMI, as VP elect; Leadership roles: NCI Steering Committee (paid), SNMMI VP elect, SNMMI Appropriate Use Criteria Author, Intersocietal Accreditation Council (all unpaid)

RC: Research funding for clinical trials from MSD Ireland, Pfizer, Daichii Sankyo, and Astra Zeneca; all to institution. Consulting for Astra Zeneca/Daichii, Gilead, Seagen, and Lilly. Travel/conference support from Novartis, Roche and Gilead.

ES: Grants from Susan G. Komen and V Foundation; Consulting for Lilly, Merck, AstraZeneca, Novartis; Travel/conference support from Curio Science, NCCN; Advisor for Cancer Awareness Network, My Beauty for Ashes (unpaid)

JR: Institutional funding from the National Cancer Institute’s National Clinical Trials Network (grant number: U10CA180794) to support my work.

CO’S: Mayo Clinic Breast Specialized Program of Research Excellence, SPORE P50CA116201, Conquer Cancer Foundation of ASCO Career Development Award 2018, Pfizer Research funding to institution AstraZeneca Research funding to institution, Honoraria to institution for Sanford Health Breast Center Symposium, Participation on DSM/Advisory Board: AstraZeneca Steering Committee (Institution), Pfizer Steering Committee (Institution), Seagen Advisory Board (Institution), AstraZeneca Advisory Board (Institution)

VS: Research grants to institution: Abbvie, Biocept, Novartis, Pfizer, Puma Biotechnology, and QUE Oncology; Non financial support: Foundation Medicine Study Assays; Chair DSMB AstraZeneca

AF: Consulting Services for ECOG/ACRIN – EAI142

AD: Institutional research support: Genetech, Norvartis, Pfizer, NeoGenomics

DM: Grants/Contracts: US NIH, Consulting Fees: GE Healthcare, Blue Earth Diagnostics, Scientific Advisory Board: ImaginAb, Reflexion, Trevarx; Trevarx – Co-founder; wife is CEO

AW: DSMB for Impassion 030

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

References

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