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First-Line Immune Checkpoint Inhibition for Advanced Non-Small-Cell Lung Cancer: State of the Art and Future Directions

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Abstract

The advent of PD-(L)1 and CTLA-4 immune check point inhibitors (CPIs) has dramatically changed the treatment landscape of advanced non-small-cell lung cancer (NSCLC). For up to a quarter of patients with advanced NSCLC, CPIs have the potential to induce durable responses with long-term survival outcomes. Since the approval of first-line pembrolizumab for patients whose tumors express a PD-L1 ≥ 50%, several pivotal first-line CPI-based phase 3 studies have been conducted investigating combination treatments combining CPIs with chemotherapy (ChT) or combining different CPIs with or without ChT. As a result, there has been an increase in front-line treatment options for advanced NSCLC, and treatment algorithms are changing very quickly. In fit patients with advanced NSCLC, combination treatments including CPI and ChT are considered the new standard of care with improved clinical outcomes. CPI combination treatments are well tolerated and quality of life also seems to be better when CPIs are implemented in the first-line setting. The aim of this review is to provide a summary of the recently published first-line phase 3 studies investigating CPIs as monotherapy or in combination with other CPIs or ChT in advanced NSCLC, and to suggest possible treatment algorithms.

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Authors and Affiliations

  1. Department of Medical Oncology, Spital STS AG, Thun, Switzerland

    Christoph Jakob Ackermann

  2. Department of Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, UK

    Helen Adderley, Ana Ortega-Franco, Adeel Khan & Raffaele Califano

  3. Department of Thoracic Oncology, Airway Research Center North (ARCN), German Center for Lung Research, LungenClinic Grosshansdorf, Grosshansdorf, Germany

    Martin Reck

  4. Department of Medical Oncology, Manchester University NHS Foundation Trust, Manchester, UK

    Raffaele Califano

  5. Division of Cancer Sciences, University of Manchester, Manchester, UK

    Raffaele Califano

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  1. Christoph Jakob Ackermann
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  2. Helen Adderley
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  3. Ana Ortega-Franco
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Correspondence to Raffaele Califano.

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Conflict of interest

Author RC has received honoraria and consultancy fees from AstraZeneca, Roche, MSD, and Bristol Myers Squibb. Author MR has received honoraria for lectures and consultancy fees from Abbvie, Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Celgene, Merck, MSD, Novartis, Pfizer, and Roche. Authors CJA, HA, AO, and AD have no conflicts of interest.

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Ackermann, C.J., Adderley, H., Ortega-Franco, A. et al. First-Line Immune Checkpoint Inhibition for Advanced Non-Small-Cell Lung Cancer: State of the Art and Future Directions. Drugs 80, 1783–1797 (2020). https://doi.org/10.1007/s40265-020-01409-6

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