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 Perol; Egbert F. Smit; Kostas Syrigos; Jan P. van Meerbeeck; Nico van Zandwijk; James Chih-Hsin Yang; Caicun Zhou; Everett Vokes

doi:10.1016/j.jtho.2016.10.003

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 journal › (Systematic) Review article › peer-review

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 language	English
Pages (from-to)	194-207
Number of pages	14
Journal	Journal of Thoracic Oncology
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/j.jtho.2016.10.003
Publication status	Published - 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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Cite this

Manegold, C., Dingemans, A.-M. C., Gray, J. E., Nakagawa, K., Nicolson, M., Peters, S., Reck, M., Wu, Y.-L., Brustugun, O. T., Crino, L., Felip, E., Fennell, D., Garrido, P., Huber, R. M., Marabelle, A., Moniuszko, M., Mornex, F., Novello, S., Papotti, M., ... Vokes, E. (2017). The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC. Journal of Thoracic Oncology, 12(2), 194-207. https://doi.org/10.1016/j.jtho.2016.10.003

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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. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.",

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",

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

year = "2017",

month = feb,

doi = "10.1016/j.jtho.2016.10.003",

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journal = "Journal of Thoracic Oncology",

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Manegold, C, Dingemans, A-MC, Gray, JE, Nakagawa, K, Nicolson, M, Peters, S, Reck, M, Wu, Y-L, Brustugun, OT, Crino, L, Felip, E, Fennell, D, Garrido, P, Huber, RM, Marabelle, A, Moniuszko, M, Mornex, F, Novello, S, Papotti, M, Perol, M, Smit, EF, Syrigos, K, van Meerbeeck, JP, van Zandwijk, N, Yang, JC-H, Zhou, C & Vokes, E 2017, 'The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC', Journal of Thoracic Oncology, vol. 12, no. 2, pp. 194-207. https://doi.org/10.1016/j.jtho.2016.10.003

TY - JOUR

T1 - The Potential of Combined Immunotherapy and Antiangiogenesis for the Synergistic Treatment of Advanced NSCLC

AU - Manegold, Christian

AU - Dingemans, Anne-Marie C.

AU - Gray, Jhanelle E.

AU - Nakagawa, Kazuhiko

AU - Nicolson, Marianne

AU - Peters, Solange

AU - Reck, Martin

AU - Wu, Yi-Long

AU - Brustugun, Odd Terje

AU - Crino, Lucio

AU - Felip, Enriqueta

AU - Fennell, Dean

AU - Garrido, Pilar

AU - Huber, Rudolf M.

AU - Marabelle, Aurelien

AU - Moniuszko, Marcin

AU - Mornex, Francoise

AU - Novello, Silvia

AU - Papotti, Mauro

AU - Perol, Maurice

AU - Smit, Egbert F.

AU - Syrigos, Kostas

AU - van Meerbeeck, Jan P.

AU - van Zandwijk, Nico

AU - Yang, James Chih-Hsin

AU - Zhou, Caicun

AU - Vokes, Everett

PY - 2017/2

Y1 - 2017/2

N2 - 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.

AB - 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.

KW - Antiangiogenesis

KW - Combination therapy

KW - Immunotherapy

KW - NSCLC

KW - CELL LUNG-CANCER

KW - ENDOTHELIAL GROWTH-FACTOR

KW - RANDOMIZED CONTROLLED-TRIAL

KW - PHASE-III TRIAL

KW - DOUBLE-BLIND

KW - PATIENTS PTS

KW - METASTATIC MELANOMA

KW - BEVACIZUMAB BEV

KW - VEGF-A

KW - TUMOR MICROENVIRONMENT

U2 - 10.1016/j.jtho.2016.10.003

DO - 10.1016/j.jtho.2016.10.003

M3 - (Systematic) Review article

C2 - 27729297

SN - 1556-0864

VL - 12

SP - 194

EP - 207

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

IS - 2

ER -