Daniel Johnathan Hughes, Gitasha Chand, Jessica Johnson, Ronan Tegala, Damion Bailey, Kathryn Adamson, Scott Edmonds, Levente K Meszaros, Amelia Elizabeth Broomfield Moore, Thubeena Manickavasagar, Susan Ndagire, Spyridon Gennatas, Alexandros Georgiou, Sharmistha Ghosh, Debra Josephs, Eleni Karapanagiotou, Emma McLean, Hong Hoi Ting, James Spicer, Vicky Goh, Gary J R Cook
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引用次数: 0
Abstract
Background: Programmed death-ligand 1 (PD-L1) immunohistochemistry is a predictive biomarker for anti-PD-(L)1 therapy in non-small cell lung cancer (NSCLC). It is not a reliable predictor of clinical benefit with non-invasive imaging providing a potential solution. We present the PECan study, the aim of which to assess the relationship of [99mTc]-labeled anti-PD-L1 single-domain antibody (NM-01) single-photon emission computed tomography (SPECT)/CT with metabolic response to anti-PD-(L)1.
Methods: PD-L1 tumour proportion score (TPS) measured using SP263 assay. [99mTc]NM-01 SPECT/CT and [18F]FDG PET/CT performed before and 9-weeks following pembrolizumab with/without chemotherapy in patients with advanced NSCLC. Tumor (T) to blood pool (BP) maximum region of interest (ROImax) measurements performed in primary and metastatic lesions using SPECT/CT images.
Results: Fifteen patients were included (median age 63 years, 9 male). Intertumoural heterogeneity evident in 10(67%) patients. Mean [99mTc]NM-01 T:BP demonstrated moderate correlation with PD-L1 TPS (r = 0.45, p < 0.05). Depth of [18F]FDG PET/CT metabolic response at 9-weeks (n = 13), correlated strongly with baseline [99mTc]NM-01 T:BP (r = -0.73, p < 0.05), but only moderately with PD-L1 TPS (r = -0.46, p = 0.06).
Conclusion: [99mTc]NM-01 SPECT/CT allows non-invasive quantification of PD-L1 in primary tumour and metastases in NSCLC. [99mTc]NM-01 uptake moderately correlates with PD-L1 immunohistochemistry, determines heterogeneity, and is associated with early metabolic response to anti-PD-1 pembrolizumab.
Clinical trials registration: PD-L1 Expression in Cancer (PECan) study (NCT04436406), registered 18 June 2020 https://clinicaltrials.gov/ct2/show/NCT04436406.
期刊介绍：
The British Journal of Cancer is one of the most-cited general cancer journals, publishing significant advances in translational and clinical cancer research.It also publishes high-quality reviews and thought-provoking comment on all aspects of cancer prevention,diagnosis and treatment.
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