Feasibility of [89Zr]Zr-Atezolizumab Immuno-PET for PD-L1 Quantification in the Clinical Work-up of Metastatic Triple-Negative Breast Cancer

Abstract

Immune checkpoint inhibitors combined with chemotherapy are established as first-line therapy for patients with programmed death ligand 1 (PD-L1)-positive metastatic triple-negative breast cancer (mTNBC). We evaluated whether immuno-PET using [⁸⁹Zr]Zr-atezolizumab could more accurately identify patients with mTNBC who may benefit from immune checkpoint inhibitor therapy. Methods: Three patients with mTNBC underwent [⁸⁹Zr]Zr-atezolizumab PET/CT followed by a biopsy of a targeted metastatic lesion. Patients received atezolizumab plus chemotherapy if either immunohistochemistry of the metastatic lesion or PET imaging showed PD-L1 positivity. Results: All patients had tracer-avid metastatic lesions on PET. Two of 3 biopsied, tracer-avid lesions were PD-L1 negative on immunohistochemistry. Intraindividual heterogeneity in tracer uptake was noted. All patients were treated with atezolizumab plus chemotherapy, with all demonstrating an initial response. Conclusion: A work-up with [⁸⁹Zr]Zr-atezolizumab immuno-PET is clinically feasible. This molecular imaging-based strategy holds potential as a noninvasive tool to more accurately identify patients with mTNBC who may benefit from immune checkpoint inhibitor therapy.

Trial registration: ClinicalTrials.gov NCT05742269.

Keywords: PD-L1; [89Zr]Zr-atezolizumab; breast; immuno-PET; mTNBC.