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First-Line Treatment of Non-Small-Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors

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Abstract

Treatment of advanced-stage or metastatic non-small-cell lung cancers (NSCLCs) without EGFR mutations or ALK rearrangements, which can now be treated with molecularly targeted therapies, had been based on cytotoxic chemotherapy for a long time. Immune checkpoint inhibitors (ICIs), notably antibodies directed against programmed cell-death protein-1 (PD-1) and its ligand (PD-L1) have transformed therapeutic standards in thoracic oncology. These ICIs are now the reference second-line treatment and numerous phase III trials have examined their efficacy in treatment-naïve patients. First-line pembrolizumab monotherapy was validated for patients with ≥ 50% of tumor cells expressing PD-L1; pembrolizumab, atezolizumab, and nivolumab have obtained good outcomes in combination with chemotherapy or another immunotherapy. However, in this context, other phase III trials yielded negative findings for nivolumab alone (CheckMate-026) or in combination (MYSTIC trial). Biomarkers, such as PD-L1 and the tumor mutation burden (TMB), enable better selection of patients who should benefit the most from first-line ICI use.

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Authors and Affiliations

  1. Service de Pneumologie, Hôpital d’Instruction des Armées Percy, 106, avenue Henri-Barbusse, 92140, Clamart Cedex, France

    Olivier Bylicki & Jacques Margery

  2. Department of Respiratory Diseases, Hôpital d’Instruction des Armées Saint-Anne, Toulon, France

    Helene Barazzutti & Nicolas Paleiron

  3. Service de Pneumologie, Centre Hospitalier Intercommunal Creteil, 40 avenue de Verdun, 94010, Creteil, France

    Jean-Baptiste Assié & Christos Chouaïd

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  1. Olivier Bylicki
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  2. Helene Barazzutti
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Correspondence to Olivier Bylicki or Christos Chouaïd.

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Christos Chouaid declares that in the past 5 years, he received fees for attending scientific meetings, speaking, organizing research or consulting from AstraZeneca, Boehringer Ingelheim, GSK, Roche, Sanofi Aventis, BMS, MSD, Lilly, Novartis, and Amgen. Olivier Bylicki, Nicolas Paleiron, Hélène Barazzutti, Jean Baptiste Assié, and Jacques Margery declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Bylicki, O., Barazzutti, H., Paleiron, N. et al. First-Line Treatment of Non-Small-Cell Lung Cancer (NSCLC) with Immune Checkpoint Inhibitors. BioDrugs 33, 159–171 (2019). https://doi.org/10.1007/s40259-019-00339-4

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