Abstract P3-02-06: A phase II study of 68Ga-ABY-025 PET for non-invasive quantification of HER2 expression in breast cancer

Abstract Introduction/Aim: 68Ga-ABY-025 is a small-protein HER2-binder which has shown promising results in evaluating HER2 receptor status in earlier studies in breast cancer (BC). The aim of the current study was to investigate the role of 68Ga-ABY-025 PET imaging in relation to histopathology and treatment response. Methods: This single-center Phase II study consecutively included neoadjuvant patients with stage 2/3 BC (n=22) and recurrent metastatic BC (rMBC, n=18). All patients had at least one HER2-positive/borderline biopsy before inclusion and underwent 68Ga-ABY-025 PET at baseline followed by FDG PET/CT and biopsies for pathology analysis as part of study. FDG PET/CT was repeated after 2 cycles of treatment and glycolytic tumor burden (FDG2-FDG1)/FDG1) was calculated for up to five largest lesions in each patient. A reduction in glycolytic tumor burden >30% was considered good metabolic response. Uptake values (ABY-SUV) from 68Ga-ABY-025 PET in tumor lesions were compared with standard pathology analysis of tumor biopsies. Data was evaluated using regression and ROC analysis. Results: Biopsies for HER2 showed 32 positive, 3 borderline and 5 negative lesions. 68Ga-ABY-025 PET produced high-contrast images with ABY-SUV ranging from 0 to 50. Correlation of ABY-SUV and HER2 score from biopsies did not reach significance. HER2-targeted therapy in stage 2/3 BC resulted in a larger metabolic response (mean reduction of glycolytic tumor burden 70±26%) than in rMBC (mean reduction 25±61%, p<0.001). ABY-SUV correlated negatively with change in glycolytic tumor burden (p<0.0001) and ABY-SUV>6.0 predicted good metabolic response in soft-tissue tumors (AUC 0.82, 95% confidence interval 0.75-0.89, p<0.0001), corrected for neoadjuvant/recurrent setting. Using this cut-off, ABY SUV and invasive HER2 score were discordant in 12 of 40 patients (30%) - 6 with stage 2/3 BC and 6 with rMBC. Of the discordant cases, 68Ga-ABY-025 PET predicted the response correct in 7 cases (3 with stage 2/3 BC and 4 with rMBC) compared to biopsy-based pathology with correct prediction in 5 cases. Conclusion: 68Ga-ABY-025 PET is a potentially useful non-invasive indicator of in-vivo HER2 receptor status in breast cancer and might predict early response to HER2-targeted therapies. A larger multi-center study has been initiated to confirm these results. Citation Format: Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y Frejd, Johan Hartman, Victor Iyer, Mark Lubberink, Irina Velikyan, Jens Sörensen. A phase II study of 68Ga-ABY-025 PET for non-invasive quantification of HER2 expression in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-02-06.