Despite these limitations, PD-L1 remains the only predictive biomarker available in clinical practice thus far, and PD-L1 testing is required for immunotherapy selection. Finally, PD-L1 varies substantially across different anatomical sites and changes during the clinical course. Furthermore, it has been observed that patients with PD-L1 negative tumours can also get benefit of ICI strategy. However, PD-L1 is not the optimal or perfect predictive biomarker as unfortunately there is still a subset of patients who do not benefit of ICI despite having tumours with high PD-L1 expression. Of note PD-L1 expression in immune cells has also been correlated with ICI efficacy. The study revealed that three out of the five IHC assays for assessing PD-L1 expression were closely aligned on tumour cell staining (22C3, 28–8, and SP263 assays), whereas the SP142 assay exhibited fewer stained tumour cells overall, and higher sensitivity with the 73–10 assay to detect PD-L1 expression on thymic carcinomas. However, as different immunohistochemistry (IHC) assays exist for assessing PD-L1 expression, reporting discordant results in some clinical situations, the Blueprint phase 2 PD-L1 IHC Assay Comparison Project was launched to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials. Indeed, the survival benefit with ICI seems higher as higher is the PD-L1 expression. In NSCLC, PD-L1 expression has been associated with greatly improved overall survival under ICI. The two most explored predictive biomarkers are PD-L1 expression and tumour mutational burden (TMB). A special focus on the immune context of “rare” thoracic tumours (SCLC, MPM and TET) will be also provided, in order to discuss the space for immunotherapy in these diseases.ĭealing with biomarkers in advanced NSCLC: PD-L1īetter predictors for response to immunotherapy are critical for its optimal use, and different predictive biomarkers have been tested. Here we aim to review the efficacy of ICI in thoracic malignancies either in monotherapy or in combination, according to predictive biomarkers, and to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approvals of treatment strategies. Likewise, ICIs have also being tested in malignant pleural mesothelioma (MPM) and thymic epithelial tumours (TET) with promising activity. ICI strategy have also modified the therapeutic strategy in first-line setting in metastatic small-cell lung cancer (SCLC) patients, being the new standard of care worldwide, although the magnitude of benefit does not mirror the one reported in NSCLC. In advanced non-small cell lung cancer (NSCLC) patients this shift in the treatment paradigm has mainly been driven in part by long term overall survival benefit and durable responses with these drugs, which occurred regardless of the treatment line status and also in PD-L1 unselected NSCLC patients. Over the last decade, starting from the initial approval of cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitors in metastatic melanoma in 2011, programmed death (ligand) 1 (PD-(L)1) inhibitors are now a routine part of treatment for more than 20 different indications. The advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm for multiple cancer types, including thoracic malignancies. We address the efficacy of these agents, especially in NSCLC according to PD-L1 expression and histologic subtype. In this review, we aim to review the efficacy of ICI in thoracic malignancies either in monotherapy or in combination, according to predictive biomarkers, and to the US Food and Drug Administration and the European Medicines Agency approvals of treatment strategies. This phenomenon is of huge relevance as both SCLC and MPM were considered orphan diseases without any significant improvement in the therapeutic strategy in the first-line setting during the last 15 years. ICIs therapies have also modified the therapeutic strategy in first-line setting in metastatic small-cell lung cancer (SCLC) patients as well as in malignant pleural mesothelioma (MPM) improving the overall survival compared with standard treatment. In advanced non-small cell lung cancer (NSCLC), ICIs have shifted treatment paradigm and improved overall survival reaching almost one-third of patients alive at 5 years.
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