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Targeting the PD-1/PD-L1 Immune Checkpoint in EGFR-Mutated or ALK-Translocated Non-Small-Cell Lung Cancer

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Abstract

Immune checkpoint inhibitors, notably antibodies targeting programmed death–1 (PD-1) and programmed death ligand–1 (PD-L1), have modified the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Several PD-1/PD-L1 inhibitors have been approved by health authorities for this indication and others are in clinical development. However, only a subset of patients truly benefits from these agents. For patients with mutated EGFR or translocated ALK NSCLC, for whom an immune checkpoint inhibitor can be prescribed after progression on tyrosine kinase inhibitors and chemotherapy, information is scarce and sometimes contradictory. Phase III randomized clinical trials have evaluated different immune checkpoint inhibitors (nivolumab, pembrolizumab, atezolizumab) vs. chemotherapy as second- or subsequent-line therapy in NSCLC, but included very few patients with EGFR/ALK-positive disease. Subgroup analyses found that these patients did not benefit from immune checkpoint inhibitors. Retrospective data show progression-free survival lasting only 1.2–2.1 months. Preclinical data suggested a lower expression of PD-L1 in EGFR/ALK-positive patients compared to EGFR/ALK-negative patients. Our objective herein is to provide an up-to-date review of available data from the various publications on the impact of immune checkpoint inhibitors in patients with EGFR/ALK-positive NSCLC.

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Authors and Affiliations

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

    Olivier Bylicki & Jacques Margery

  2. Service des Maladies Respiratoires, Hôpital d’Instruction des Armées Clermont Tonnerre, Brest, France

    Nicolas Paleiron

  3. Clinique Pneumologique, Rouen University Hospital, Rouen, France

    Florian Guisier

  4. Centre Hospitalier Universitaire du Cluzeau de Limoges, Limoges, France

    Alain Vergnenegre

  5. Service de Pneumologie, CHU de Brest, Brest, France

    Gilles Robinet

  6. Service de Pneumologie et Oncologie Thoracique, Hôpital François-Quesnay, Mantes-la-Jolie, France

    Jean-Bernard Auliac

  7. Department of Oncology, François-Baclesse Cancer Center, Caen, France

    Radj Gervais

  8. Service de Pneumologie, CHI Créteil, Créteil, France

    Christos Chouaid

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  1. Olivier Bylicki
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This academic review was conducted by the Groupe Français de Pneumo-Cancérologie (GFPC).

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Bylicki, O., Paleiron, N., Margery, J. et al. Targeting the PD-1/PD-L1 Immune Checkpoint in EGFR-Mutated or ALK-Translocated Non-Small-Cell Lung Cancer. Targ Oncol 12, 563–569 (2017). https://doi.org/10.1007/s11523-017-0510-9

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