89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer

Bensch, Frederike; Veen, Elly L. van der; Hooge, Marjolijn N. Lub-de; Jorritsma-Smit, Annelies; Boellaard, Ronald; Kok, Iris C.; Oosting, Sjoukje F.; Schröder, Carolina P.; Hiltermann, T Jeroen N; Wekken, Anthonie J. van der; Groen, Harry J.M.; Kwee, Thomas C.; Elias, Sjoerd G.; Gietema, Jourik A.; Bohórquez, Sandra Sanabria; Crespigny, Alex de; Williams, Simon P.; Mancao, Christoph; Brouwers, Adrienne H.; Fine, Bernard M.; Vries, Elisabeth G.E. de

doi:10.1038/s41591-018-0255-8

Cited by 552 publications

(559 citation statements)

References 40 publications

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“…Furthermore, response to treatment was also influenced by metastatic site. Also, strengthening the observations published by Bensch et al . which revealed that the maximal tumoral uptake of 89 Zr‐atezolizumab was observed by liver and nodal lesions, their occurrence also correlated with survival in this study.…”

Section: Discussionsupporting

confidence: 91%

Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non‐small cell lung cancer (NSCLC) compared with chemotherapy (Quijote‐CLICaP)

et al. 2019

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Background: To compare survival outcomes of patients with advanced or metastatic non-small cell lung cancer (NSCLC) who received immunotherapy as first-, second-or beyond line, versus matched patients receiving standard chemotherapy with special characterization of hyperprogressors. Methods: A retrospective cohort study of 296 patients with unresectable/metastatic NSCLC treated with either, first-, second-, third-or fourth-line of immunotherapy was conducted. A matched comparison with a historical cohort of first-line chemotherapy and a random forest tree analysis to characterize hyperprogressors was conducted. Results: Median age was 64 years (range 34-90), 40.2% of patients were female. A total of 91.2% of patients had an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 1. Immunotherapy as first-line was given to 39 patients (13.7%), second-line to 140 (48.8%), and as third-line and beyond to 108 (37.6%). Median overall survival was 12.7 months (95% CI 9.67-14 months) and progression-free survival (PFS) of 4.27 months (95% CI 3.97-5.0). Factors associated with increased survival included treatment with immunotherapy as first-line (P < 0.001), type of response (P < 0.001) and PD-L1 status (P = 0.0039). Compared with the historical cohort, immunotherapy proved to be superior in terms of OS (P = 0.05) but not PFS (P = 0.2). A total of 44 hyperprogressors were documented (19.8%,.1%]). Leukocyte count over 5.300 cells/dL was present in both hyperprogressors and long-term responders. Conclusions: Patients who receive immune-checkpoint inhibitors as part of their treatment for NSCLC have better overall survival (OS) compared with matched patients treated with standard chemotherapy, regardless of the line of treatment.

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Section: Discussionsupporting

confidence: 91%

Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non‐small cell lung cancer (NSCLC) compared with chemotherapy (Quijote‐CLICaP)

et al. 2019

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“…Molecular imaging techniques using radioactive tracers that target PD-1 and PD-L1 have also been explored in a preclinical study [81,82]. A first-in-human study using PET with 89 Zr-labeled atezolizumab has been conducted in 22 patients to predict response to PD-L1 treatment [83]. The authors showed a significant correlation between 89 Zr-labeled atezolizumab uptake and patient outcomes in terms of progression-free and overall survival.…”

Section: Other Toxicitiesmentioning

confidence: 99%

Imaging of tumour response to immunotherapy

et al. 2020

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A wide range of cancer immunotherapy approaches has been developed including non-specific immune-stimulants such as cytokines, cancer vaccines, immune checkpoint inhibitors (ICIs), and adoptive T cell therapy. Among them, ICIs are the most commonly used and intensively studied. Since 2011, these drugs have received marketing authorisation for melanoma, lung, bladder, renal, and head and neck cancers, with remarkable and long-lasting treatment response in some patients. The novel mechanism of action of ICIs, with immune and T cell activation, leads to unusual patterns of response on imaging, with the advent of so-called pseudoprogression being more pronounced and frequently observed when compared to other anticancer therapies. Pseudoprogression, described in about 2-10% of patients treated with ICIs, corresponds to an increase of tumour burden and/or the appearance of new lesions due to infiltration by activated T cells before the disease responds to therapy. To overcome the limitation of response evaluation criteria in solid tumors (RECIST) to assess these specific changes, new imaging criteria-so-called immune-related response criteria and then immune-related RECIST (irRECIST)-were proposed. The major modification involved the inclusion of the measurements of new target lesions into disease assessments and the need for a 4-week re-assessment to confirm or not confirm progression. The RECIST working group introduced the new concept of "unconfirmed progression", into the irRECIST. This paper reviews current immunotherapeutic approaches and summarises radiologic criteria to evaluate new patterns of response to immunotherapy. Furthermore, imaging features of immunotherapy-related adverse events and available predictive biomarkers of response are presented.

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“…New approaches for evaluating PD-L1 expression that are being developed include noninvasive nuclear imaging approaches, which may allow unbiased whole-body imaging of PD-L1 expression that can be followed over time (Kumar et al 2019, Niemeijer et al 2018. Initial studies using zirconium 89-labeled atezolizumab (Bensch et al 2018) suggest that this approach may be more predictive than IHC-or RT-PCR-based assays.…”

Section: New Approachesmentioning

confidence: 99%

Biomarkers for Response to Immune Checkpoint Blockade

Ganesan

Mehnert²

2020

Annu. Rev. Cancer Biol.

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Immune checkpoint blockade (ICB) has significant clinical activity in diverse cancer classes and can induce durable remissions in even refractory advanced disease. However, only a minority of cancer patients treated with ICB have long-term benefits, and ICB treatment is associated with significant, potentially life-threatening, autoimmune side effects. There is a great need to develop biomarkers of response to guide patient selection to maximize the chance of benefit and prevent unnecessary toxicity, and current biomarkers do not have optimal positive or negative predictive value. A variety of potential biomarkers are currently being developed, including those based on assessment of checkpoint protein expression, evaluation of tumor-intrinsic features including mutation burden and viral infection, evaluation of features of the tumor immune microenvironment including nature of immune cell infiltration, and features of the host such as composition of the gut microbiome. Better understanding of the underlying fundamental mechanisms of immune response and resistance to ICB, along with the use of complementary assays that interrogate distinct features of the tumor, the tumor microenvironment, and host immune system, will allow more precise use of these therapies to optimize patient outcomes.

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89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer

Cited by 552 publications

References 40 publications

Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non‐small cell lung cancer (NSCLC) compared with chemotherapy (Quijote‐CLICaP)

Immunotherapy at any line of treatment improves survival in patients with advanced metastatic non‐small cell lung cancer (NSCLC) compared with chemotherapy (Quijote‐CLICaP)

Imaging of tumour response to immunotherapy

Biomarkers for Response to Immune Checkpoint Blockade

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