482P - Precision imaging with human epidermal growth factor receptor 2-positron emission tomography (HER2-PET) for refined treatment selection in patients with HER2-low breast cancer

Background

HER2-low metastatic breast cancer (mBC) is a clinically relevant subgroup with promising treatment options. Challenges relate to establishing HER2-low status when biopsies are not feasible, and little is known about disease heterogeneity. PET-imaging with a HER2-specific tracer could shed light on these issues.

Methods

At the Karolinska Comprehensive Cancer Center in Stockholm, Sweden we conducted a proof-of-concept prospective imaging study with the [⁶⁸Ga]Ga-ABY-025 tracer in patients with mBC with a previous HER2-low tumor biopsy, who were scheduled for a new line of systemic therapy. A HER2-PET and tumor biopsy (immunohistochemistry [IHC] and in situ hybridization [ISH]) were performed. The study was funded by the Swedish Breast Cancer Society and Stockholm’s Region.

Results

Seventeen patients were informed, ten patients provided written consent and in ten, paired PET and biopsy results are available (Table). No unexpected side effects were noted. In all, HER2-PET revealed areas with [⁶⁸Ga]Ga-ABY-025 maximal Standardized Uptake Value (SUV_max) higher than background ratio. HER2-low status was confirmed in tumor biopsies in eight, whereas two patients had HER2 0 in a tumor lesion that was avid on HER2-PET. Substantial heterogeneity was observed in [⁶⁸Ga]Ga-ABY-025 uptake between different lesions within the same patient. Table: 482P

* measured on healthy liver tissue

Conclusions

The visualization of HER2-expressing mBC with [⁶⁸Ga]Ga-ABY-025 PET/CT is feasible and safe. An intriguing finding is the fact that we noted tracer uptake in lesions that are HER2 0. A continued study is planned where patients with HER2-low mBC are selected for HER2-antibody drug conjugate based on HER2-status on PET and/or IHC.

Clinical trial identification

NCT05619016 EU CT 2022-500448-39-00.

Editorial acknowledgement

Legal entity responsible for the study

Karolinska University Hospital/Region Stockholm.

Funding

Grants from the Swedish government under the ALF-agreement (SLL20200025), Sjöberg Foundation (929649), and the Swedish Breast Cancer Society (190850).

Disclosure

N. Brun, F. Y. Frejd: Financial Interests, Personal, Full or part-time Employment: Affibody AB; Financial Interests, Personal, Leadership Role: Affibody AB; Financial Interests, Personal, Ownership Interest: Affibody AB. T.A. Tran: Financial Interests, Personal, Stocks or ownership: Diaprost; Financial Interests, Personal, Research Funding: Affibody AB; Financial Interests, Personal, Royalties: Diaprost. All other authors have declared no conflicts of interest.