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      Profile of atezolizumab in the treatment of metastatic non-small-cell lung cancer: patient selection and perspectives

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          Abstract

          Programed cell death-1/programed death ligand-1 (PD-1/PD-L1) blockade represents an affirmed reality in the treatment of advanced non-small-cell lung cancer (NSCLC) patients. Atezolizumab, an anti-PD-L1 agent, figures among the drugs that provide previously unenvisaged outcomes in the pretreated setting of metastatic NSCLC. Increasing evidence vouches for the early administration of PD-1/PD-L1 blockers in untreated patients, encompassing atezolizumab combinations with chemotherapy and the anti-angiogenic agent bevacizumab. Moreover, the development of atezolizumab allowed to derive several hints regarding clinical and immunological factors predictive of its activity and efficacy, some of them exclusive among this class of drugs. This review provides an overview of atezolizumab development throughout clinical trials toward its applicability in the routine practice, with a particular focus on patient selection based on clinical and immune-related factors.

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          Most cited references 45

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          Checkpoint Inhibitors in Metastatic EGFR-Mutated Non-Small Cell Lung Cancer-A Meta-Analysis.

          We performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC.
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            Programmed Death-Ligand 1 Immunohistochemistry Testing: A Review of Analytical Assays and Clinical Implementation in Non–Small-Cell Lung Cancer

            Purpose Three programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for treatment of non-small-cell lung cancer (NSCLC). Treatment with pembrolizumab in NSCLC requires PD-L1 immunohistochemistry (IHC) testing. Nivolumab and atezolizumab are approved without PD-L1 testing, though US Food and Drug Administration-cleared complementary PD-L1 tests are available for both. PD-L1 IHC assays used to assess PD-L1 expression in patients treated with programmed death-1/PD-L1 inhibitors in clinical trials include PD-L1 IHC 28-8 pharmDx (28-8), PD-L1 IHC 22C3 pharmDx (22C3), Ventana PD-L1 SP142 (SP142), and Ventana PD-L1 SP263 (SP263). Differences in antibodies and IHC platforms have raised questions about comparability among these assays and their diagnostic use. This review provides practical information to help physicians and pathologists understand analytical features and comparability of various PD-L1 IHC assays and their diagnostic use. Methods We reviewed and summarized published or otherwise reported studies (January 2016 to January 2017) on clinical trial and laboratory-developed PD-L1 IHC assays (LDAs). Studies assessing the effect of diagnostic methods on PD-L1 expression levels were analyzed to address practical issues related to tissue samples used for testing. Results High concordance and interobserver reproducibility were observed with the 28-8, 22C3, and SP263 clinical trial assays for PD-L1 expression on tumor cell membranes, whereas lower PD-L1 expression was detected with SP142. Immune-cell PD-L1 expression was variable and interobserver concordance was poor. Inter- and intratumoral heterogeneity had variable effects on PD-L1 expression. Concordance among LDAs was variable. Conclusion High concordance among 28-8, 22C3, and SP263 when assessing PD-L1 expression on tumor cell membranes suggests possible interchangeability of their clinical use for NSCLC but not for assessment of PD-L1 expression on immune cells. Development of LDAs requires stringent standardization before their recommendation for routine clinical use.
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              Incidence of pneumonitis with use of PD-1 and PD-L1 inhibitors in non-small cell lung cancer: A Systematic Review and Meta-analysis of trials.

              PD-1/PD-L1 inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis, and differences according to type of inhibitors and prior chemotherapy use.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2018
                10 September 2018
                : 12
                : 2857-2873
                Affiliations
                Medical Oncology Unit, University Hospital of Parma, Parma, Italy, francescofacchinetti2@ 123456gmail.com
                Author notes
                Correspondence: Francesco Facchinetti, Medical Oncology Unit, University Hospital of Parma, Via Gramsci, 14, 43126 Parma, Italy, Tel +39 052 170 2316, Fax +39 052 199 5448, Email francescofacchinetti2@ 123456gmail.com
                Article
                dddt-12-2857
                10.2147/DDDT.S124380
                6137949
                © 2018 Facchinetti et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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