Immune Checkpoint and Anti-Angiogenic Antibodies for the Treatment of Non-Small Cell Lung Cancer in the European Union and United States

Several types of antibodies (Abs) are currently used in non-small cell lung cancer (NSCLC). Anti-angiogenic and immune checkpoint inhibitor (ICI) Abs are the most frequent treatments used alone or with chemotherapy in metastatic NSCLC, for the front line and beyond. Considering the many therapeutic options for locally advanced and metastatic lung cancer and differences in use according to geographic area, we present here a comprehensive review of the marketed ICI and anti-angiogenic Abs approved in the European Union (EU) and the US to treat locally advanced and metastatic NSCLC patients. We briefly describe the different molecules and their development in thoracic oncology and compare pharmacokinetic data, processing decision algorithms and marketing authorizations by the EMA and US Food and Drug Administration (FDA).

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Current topics of immune checkpoint inhibitors in perioperative and locally advanced non-small cell lung cancer

Annals of Oncology ◽

10.1093/annonc/mdy354.001 ◽

2018 ◽

Vol 29 ◽

pp. vii15

Author(s):

Hidehito Horinouchi

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Locally Advanced ◽

Small Cell ◽

Small Cell Lung

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PD-L1 expression testing in non-small cell lung cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835918763493 ◽

2018 ◽

Vol 10 ◽

pp. 175883591876349 ◽

Cited By ~ 57

Author(s):

Cristina Teixidó ◽

Noelia Vilariño ◽

Roxana Reyes ◽

Noemí Reguart

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Locally Advanced ◽

Small Cell ◽

Small Cell Lung

In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors, fundamentally those that act by blocking the programmed cell death receptor-1 (PD-1) and its ligand the programmed cell death ligand-1 (PD-L1) have emerged as novel treatment strategies in NSCLC, demonstrating undoubted superiority over chemotherapy in terms of efficacy. Several of these immune checkpoint modulators have recently gained regulatory approval for the treatment of advanced NSCLC, such as nivolumab, atezolizumab and pembrolizumab in first-line (only the latter) and second-line settings, and more recently, durvalumab as maintenance after chemoradiotherapy in locally advanced disease. There is consensus that PD-L1 expression on tumor cells predicts responsiveness to PD-1 inhibitors in several tumor types. Hence PD-L1 expression evaluated by immunohistochemistry (IHC) is currently used as a clinical decision-making tool to support the use of checkpoint inhibitors in NSCLC patients. However, the value of PD-L1 as the ‘definitive’ biomarker is controversial as its testing is puzzled by multiple unsolved issues such as the use of different staining platforms and antibodies, the type of cells in which PD-L1 is assessed (tumor versus immune cells), thresholds used for PD-L1-positivity, or the source and timing for sample collection. Therefore, newer biomarkers such as tumor mutation burden and neoantigens as well as biomarkers reflecting host environment (microbiome) or tumor inflamed microenvironment (gene expression signatures) are being explored as more reliable and accurate alternatives to IHC for guiding treatment selection with checkpoint inhibitors in NSCLC.

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