In a letter published on 26 November 2018 in the Nature Medicine, Elisabeth G. E. de Vries of the Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands and colleagues presented the initial results from a first-in-human study to assess the feasibility of molecular positron emission tomography (PET) imaging with zirconium-89-labeled atezolizumab and to test its potential to predict response to PD-L1 blockade.
The authors wrote in the study background that PD-(L)1 blockade is effective only in a subset of patients with several cancer types, but predicting patient benefit by using approved diagnostics is not exact, as some patients with PD-L1-negative tumours also show clinical benefit. Furthermore, all biopsy-based tests are subject to the errors and limitations of invasive tissue collection.
Preclinical studies of PET imaging with antibodies to PD-L1 suggested that this imaging method might be an approach to select the patients. However, such technique requires substantial clinical development and validation.
In the first-in-human study, the authors assessed the feasibility of imaging with zirconium-89-labeled atezolizumab, including biodistribution. They also tested its potential to predict response to anti-PD-L1 therapy.
The investigators performed imaging in 22 patients in three tumour types before the start of therapy with atezolizumab. They found that the PET signal, a function of tracer exposure and target expression, was high in lymphoid tissues and at sites of inflammation. In tumours, uptake was generally high but heterogeneous, varying within and among lesions, patients, and tumour types.
Clinical responses in the patients were better correlated with pre-treatment PET signal than with immunohistochemistry- or RNA-sequencing-based predictive biomarkers, encouraging further development of molecular PET imaging for assessment of PD-L1 status and clinical response prediction.
The RNA-sequencing dataset is available through GEO. The data are annotated with a short summary and a description of the study design and can be freely downloaded via the GEO website. Clinical details of the cases and laboratory data, restricted to non-identifying data owing to privacy concerns, can be requested from the corresponding author of the study.
This work was supported by the Dutch Cancer Society grant, the ERC Advanced grant, a personal Dutch Cancer Society fellowship, and a research grant from Hoffmann–La Roche/Genentech, which was made available to the University Medical Center Groningen.
Bensch F, van der Veen EL, Lub-de-Hooge MN, et al. 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nature Medicine; Published 26 November 2018. DOI: https://doi.org/10.1038/s41591-018-0255-8