The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC

Christian Manegold*, Anne-Marie C. Dingemans, Jhanelle E. Gray, Kazuhiko Nakagawa, Marianne Nicolson, Solange Peters, Martin Reck, Yi-Long Wu, Odd Terje Brustugun, Lucio Crino, Enriqueta Felip, Dean Fennell, Pilar Garrido, Rudolf M. Huber, Aurelien Marabelle, Marcin Moniuszko, Francoise Mornex, Silvia Novello, Mauro Papotti, Maurice PerolEgbert F. Smit, Kostas Syrigos, Jan P. van Meerbeeck, Nico van Zandwijk, James Chih-Hsin Yang, Caicun Zhou, Everett Vokes

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

138 Citations (Web of Science)

Abstract

Over the past few years, there have been considerable advances in the treatments available to patients with metastatic or locally advanced NSCLC, particularly those who have progressed during first-line treatment. Some of the treatment options available to patients are discussed here, with a focus on checkpoint inhibitor immunotherapies (nivolumab and pembrolizumab) and antiangiogenic agents (bevacizumab, ramucirumab, and nintedanib). It is hypothesized that combining immunotherapy with antiangiogenic treatment may have a synergistic effect and enhance the efficacy of both treatments. In this review, we explore the theory and potential of this novel treatment option for patients with advanced NSCLC. We discuss the growing body of evidence that proangiogenic factors can modulate the immune response (both by reducing T-cell infiltration into the tumor microenvironment and through systemic effects on immune-regulatory cell function), and we examine the preclinical evidence for combining these treatments. Potential challenges are also considered, and we review the preliminary evidence of clinical efficacy and safety with this novel combination in a variety of solid tumor types. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)194-207
Number of pages14
JournalJournal of Thoracic Oncology
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 2017

Keywords

  • Antiangiogenesis
  • Combination therapy
  • Immunotherapy
  • NSCLC
  • CELL LUNG-CANCER
  • ENDOTHELIAL GROWTH-FACTOR
  • RANDOMIZED CONTROLLED-TRIAL
  • PHASE-III TRIAL
  • DOUBLE-BLIND
  • PATIENTS PTS
  • METASTATIC MELANOMA
  • BEVACIZUMAB BEV
  • VEGF-A
  • TUMOR MICROENVIRONMENT

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