title: The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC.
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.
authors.affiliation: Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany. Electronic address: prof.manegold@t-online.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Manegold
authors.affiliation: Department of Pulmonary Diseases, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Anne-Marie C
authors.initials: AC
authors.lastname: Dingemans
authors.affiliation: Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Jhanelle E
authors.initials: JE
authors.lastname: Gray
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Oncology Department, Aberdeen Royal Infirmary, Aberdeen, United Kingdom.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nicolson
authors.affiliation: Department of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.affiliation: Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reck
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Odd Terje
authors.initials: OT
authors.lastname: Brustugun
authors.affiliation: Medical Oncology Department, Perugia University Medical School, Perugia, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.affiliation: Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Barcelona, Spain.
authors.forename: Enriqueta
authors.initials: E
authors.lastname: Felip
authors.affiliation: Department of Oncology, University of Leicester and Leicester University Hospitals, Leicester, United Kingdom.
authors.forename: Dean
authors.initials: D
authors.lastname: Fennell
authors.affiliation: Servicio de Oncología Médica, IRYCIS Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.affiliation: Ludwig-Maximilians-Universität München, University Hospital, Division of Respiratory Medicine and Thoracic Oncology, Münich, Germany.
authors.forename: Rudolf M
authors.initials: RM
authors.lastname: Huber
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Département d'Innovation Thérapeutique et d'Essais Précoces, INSERM U1015, Villejuif, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Marabelle
authors.affiliation: Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.affiliation: Department of Radiation Oncology, Centre Hospitalier Lyon Sud, Université Claude Bernard, Lyon, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Mornex
authors.affiliation: Department of Oncology, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Novello
authors.affiliation: Department of Oncology, University of Turin, Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.affiliation: Département de Cancérologie, Médicale Centre Léon Bérard, Lyon, France.
authors.forename: Maurice
authors.initials: M
authors.lastname: Pérol
authors.affiliation: Department of Pulmonary Diseases and Department of Thoracic Oncology, VU University Medical Centre, Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Egbert F
authors.initials: EF
authors.lastname: Smit
authors.affiliation: Oncology Unit GPP, Sotiria General Hospital, Athens University School of Medicine, Athens, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Syrigos
authors.affiliation: Thoracic Oncology, Antwerp University Hospital and Ghent University, Edegem, Belgium.
authors.forename: Jan P
authors.initials: JP
authors.lastname: van Meerbeeck
authors.affiliation: Asbestos Diseases Research Institute, University of Sydney, New South Wales, Australia.
authors.forename: Nico
authors.initials: N
authors.lastname: van Zandwijk
authors.affiliation: Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.
authors.forename: James Chih-Hsin
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Shanghai, People's Republic of China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.
authors.forename: Everett
authors.initials: E
authors.lastname: Vokes
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors
keywords: Antiangiogenesis; Combination therapy; Immunotherapy; NSCLC