Programmed death ligand 1 (PD-L1) PET/CT imaging to evaluate tumour saturation during atezolizumab treatment.

BACKGROUND: Little is known regarding tumour target saturation by the programmed death-ligand (PD-L1) antibody atezolizumab. Therefore, tumour saturation by the PD-L1 antibody atezolizumab in patients with advanced solid tumours was assessed using 89Zr-atezolizumab PET imaging. METHODS: Patients received 10 mg 89Zr-atezolizumab after the initial 2 cycles of 1200 mg atezolizumab, followed by PET/CT scans. Tracer uptake was calculated as tumour standardized uptake value (SUV)max, normal tissues SUVmean, and tumour-to-background ratio SUVmax/SUVmax tumour. Tumour biopsies were obtained around day 7 of both cycles for autoradiography and PD-L1 immunohistochemistry. Findings were compared with previously reported pretreatment 89Zr-atezolizumab PET/CT data. RESULTS: Geometric mean tumour SUVmax day 7 was similar between cycle 1 (5.5, 95% CI, 4.4-6.9) and 2 (5.4, 95% CI, 4.3-6.8, N = 13, P = 0.88). Geometric mean tumour-to-background ratio was 1.67 (95% CI, 1.15-2.41) and 1.53 (N = 11, 95% CI, 1.05-2.21, P = 0.32), respectively. Higher tumour-to-background ratios showed a positive trend with best overall response ptrend 0.069. Autoradiography signal was present in tumour biopsies. On-treatment uptake was lower in the lesions and spleen, with a higher blood pool SUVmean than pre-treatment. CONCLUSIONS: Compared to earlier reported pre-treatment 89Zr-atezolizumab PET/CT results, 89Zr-atezolizumab tumour uptake during treatment is lower, suggesting partial PD-L1 tumour saturation during atezolizumab treatment. CLINICALTRIALS: GOV: NCT02453984, NCT02478099.