Abstract
In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies. The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti–programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents. The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies. In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 914-947 |
| Number of pages | 34 |
| Journal | Journal of Thoracic Oncology |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2020 |
Keywords
- Biomarkers
- Consensus
- Immune checkpoint inhibitors
- Microbiome
- Non–small cell lung cancer
- Small cell lung cancer
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
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In: Journal of Thoracic Oncology, Vol. 15, No. 6, 06.2020, p. 914-947.
Research output: Contribution to journal › Review article › peer-review
}
TY - JOUR
T1 - Immune Checkpoint Inhibitors in Thoracic Malignancies
T2 - Review of the Existing Evidence by an IASLC Expert Panel and Recommendations
AU - Remon, Jordi
AU - Passiglia, Francesco
AU - Ahn, Myung Ju
AU - Barlesi, Fabrice
AU - Forde, Patrick M.
AU - Garon, Edward B.
AU - Gettinger, Scott
AU - Goldberg, Sarah B.
AU - Herbst, Roy S.
AU - Horn, Leora
AU - Kubota, Kaoru
AU - Lu, Shun
AU - Mezquita, Laura
AU - Paz-Ares, Luis
AU - Popat, Sanjay
AU - Schalper, Kurt A.
AU - Skoulidis, Ferdinandos
AU - Reck, Martin
AU - Adjei, Alex A.
AU - Scagliotti, Giorgio V.
N1 - Funding Information: Disclosure: Dr. Remon reports other support from MSD , Boehringer Ingelheim , Bristol-Myers Squibb , AstraZeneca , Roche Holdings, and Pfizer ; and personal fees and nonfinancial support from OSE Immunotherapeutics, outside the submitted work. Dr. Barlesi reports personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd., Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda; and grants from AbbVie , ACEA, Amgen , AstraZeneca , Bayer , Bristol-Myers Squibb , Boehringer Ingelheim , Eisai, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Genentech , Ipsen , Ignyta , Innate Pharma, Loxo, Novartis , Medimmune , Merck , MSD, Pierre Fabre , Pfizer , Sanofi -Aventis, and Takeda, outside the submitted work. Dr. Forde reports grants and personal fees from AstraZeneca / Medimmune and Bristol-Myers Squibb ; and grants from Kyowa Hakko Kirin , Novartis , and Corvus Pharmaceuticals, outside the submitted work. Dr. Garon reports personal fees from Dracen; grants and personal fees from EMD Serono and Novartis ; and grants from BMS , Eli Lilly , Merck , AstraZeneca , Genentech , Mirati Iovance, Neon, and Dynavax, outside the submitted work. Dr. Gettinger reports other support from Bristol-Myers Squibb , Nektar, Genentech / Roche , Iovance Biotherapeutics, Takeda / ARIAD , and NextCure, outside the submitted work. Dr. Goldberg reports grants and personal fees from AstraZeneca ; and personal fees from Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, and Boehringer Ingelheim, outside the submitted work. Dr. Herbst reports personal fees from AbbVie Pharmaceuticals and ARMO Biosciences; personal fees and other support from AstraZeneca , Merck and Company, Genentech / Roche , and Eli Lilly and Company ; personal fees from Biodesix, Bolt Biotherapeutics, Bristol-Myers Squibb, EMD Serrano, Genmab, Halozyme, Heat Biologics, IMAB Biopharma, Immunocore, Infinity Pharmaceuticals; other support from Junshi Pharmaceuticals; and personal fees from Loxo Oncology, Midas Health Analytics, Mirati Therapeutics, Nektar, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro, and Tocagen, outside the submitted work. Dr. Horn reports personal fees from AstraZeneca, Amgen, Genentech, Merck, Incyte, Pfizer, and Tessaro; grants and personal fees from Bristol-Myers Squibb ; personal fees from EMD Serono; grants and personal fees from Xcovery; and grants from Boehringer Ingelheim , outside the submitted work. Dr. Kubota reports grants and personal fees from Ono and Boehringer Ingelheim ; and personal fees from Chugai, MSD, AstraZeneca, Eli Lilly, Daiichi Sankyo, Bristol-Myers Squibb, Novartis, Kyowa Hakko Kirin, Eizai, and Taiho, outside the submitted work. Dr. Lu reports grants and personal fees from AstraZeneca , Roche , and Bristol-Myers Squibb , outside the submitted work. Dr. Mezquita reports personal fees from Roche Diagnostics; personal fees from Takeda; personal fees from Bristol-Myers Squibb; personal fees from Tecnofarma; other support from Bristol-Myers Squibb, Roche, and Chugai; and nonfinancial support from AstraZeneca, outside the submitted work. Dr. Paz-Ares reports other support from Genómica ; personal fees from Eli Lilly; grants and personal fees from MSD, Bristol-Myers Squibb, and AstraZeneca; personal fees from Roche, Pharmamar, Merck, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex Ipsen, Adacap, Sanofi, Bayer, and Blueprint; and other support from Altum Sequencing, outside the submitted work. Dr. Popat reports personal fees from Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Pfizer, MSD, EMD Serono, Guardant Health, AbbVie, Boehringer Ingelheim, OncLive, Medscape, and Incyte, outside the submitted work. Dr. Schalper reports personal fees from Clinica Alemana Santiago, Celgene, Moderna Therapeutics, Shattuck Labs, Pierre Fabre, AstraZeneca, Dyanamo Therapeutics, EMD Serono, Abbvie, Agenus, and Torque Therapeutics; and grants from Navigate Biopharma, Vasculox/Tioma, Tesaro, Onkaido Therapeutics, Takeda Pharmaceuticals, Surface Oncology, Pierre Fabre Research Institute, Merck, Bristol-Myers Squibb, AstraZeneca, and Eli Lilly, during the conduct of the study. In addition, Dr. Schalper has a patent (Prediction of Response to Immune-Modulatory Therapies) issued. Dr. Skoulidis reports nonfinancial support from Tango Therapeutics Inc., outside the submitted work. Dr. Reck reports personal fees from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, MSD, Novartis, Pfizer, and Roche, outside the submitted work. Dr. Scagliotti reports personal fees from AstraZeneca, Roche, and MSD during the conduct of the study; and personal fees from Eli Lilly, Takeda, and Pfizer, outside the submitted work. The remaining authors declare no conflict of interest. Funding Information: Disclosure: Dr. Remon reports other support from MSD, Boehringer Ingelheim, Bristol-Myers Squibb, AstraZeneca, Roche Holdings, and Pfizer; and personal fees and nonfinancial support from OSE Immunotherapeutics, outside the submitted work. Dr. Barlesi reports personal fees from AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann?La Roche Ltd., Novartis, Merck, MSD, Pierre Fabre, Pfizer, and Takeda; and grants from AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd., Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, and Takeda, outside the submitted work. Dr. Forde reports grants and personal fees from AstraZeneca/Medimmune and Bristol-Myers Squibb; and grants from Kyowa Hakko Kirin, Novartis, and Corvus Pharmaceuticals, outside the submitted work. Dr. Garon reports personal fees from Dracen; grants and personal fees from EMD Serono and Novartis; and grants from BMS, Eli Lilly, Merck, AstraZeneca, Genentech, Mirati Iovance, Neon, and Dynavax, outside the submitted work. Dr. Gettinger reports other support from Bristol-Myers Squibb, Nektar, Genentech/Roche, Iovance Biotherapeutics, Takeda/ARIAD, and NextCure, outside the submitted work. Dr. Goldberg reports grants and personal fees from AstraZeneca; and personal fees from Eli Lilly, Bristol-Myers Squibb, Genentech, Amgen, Spectrum, and Boehringer Ingelheim, outside the submitted work. Dr. Herbst reports personal fees from AbbVie Pharmaceuticals and ARMO Biosciences; personal fees and other support from AstraZeneca, Merck and Company, Genentech/Roche, and Eli Lilly and Company; personal fees from Biodesix, Bolt Biotherapeutics, Bristol-Myers Squibb, EMD Serrano, Genmab, Halozyme, Heat Biologics, IMAB Biopharma, Immunocore, Infinity Pharmaceuticals; other support from Junshi Pharmaceuticals; and personal fees from Loxo Oncology, Midas Health Analytics, Mirati Therapeutics, Nektar, Neon Therapeutics, NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Takeda, Tesaro, and Tocagen, outside the submitted work. Dr. Horn reports personal fees from AstraZeneca, Amgen, Genentech, Merck, Incyte, Pfizer, and Tessaro; grants and personal fees from Bristol-Myers Squibb; personal fees from EMD Serono; grants and personal fees from Xcovery; and grants from Boehringer Ingelheim, outside the submitted work. Dr. Kubota reports grants and personal fees from Ono and Boehringer Ingelheim; and personal fees from Chugai, MSD, AstraZeneca, Eli Lilly, Daiichi Sankyo, Bristol-Myers Squibb, Novartis, Kyowa Hakko Kirin, Eizai, and Taiho, outside the submitted work. Dr. Lu reports grants and personal fees from AstraZeneca, Roche, and Bristol-Myers Squibb, outside the submitted work. Dr. Mezquita reports personal fees from Roche Diagnostics; personal fees from Takeda; personal fees from Bristol-Myers Squibb; personal fees from Tecnofarma; other support from Bristol-Myers Squibb, Roche, and Chugai; and nonfinancial support from AstraZeneca, outside the submitted work. Dr. Paz-Ares reports other support from Gen?mica; personal fees from Eli Lilly; grants and personal fees from MSD, Bristol-Myers Squibb, and AstraZeneca; personal fees from Roche, Pharmamar, Merck, Novartis, Boehringer Ingelheim, Celgene, Servier, Sysmex Ipsen, Adacap, Sanofi, Bayer, and Blueprint; and other support from Altum Sequencing, outside the submitted work. Dr. Popat reports personal fees from Bristol-Myers Squibb, Roche, Takeda, AstraZeneca, Pfizer, MSD, EMD Serono, Guardant Health, AbbVie, Boehringer Ingelheim, OncLive, Medscape, and Incyte, outside the submitted work. Dr. Schalper reports personal fees from Clinica Alemana Santiago, Celgene, Moderna Therapeutics, Shattuck Labs, Pierre Fabre, AstraZeneca, Dyanamo Therapeutics, EMD Serono, Abbvie, Agenus, and Torque Therapeutics; and grants from Navigate Biopharma, Vasculox/Tioma, Tesaro, Onkaido Therapeutics, Takeda Pharmaceuticals, Surface Oncology, Pierre Fabre Research Institute, Merck, Bristol-Myers Squibb, AstraZeneca, and Eli Lilly, during the conduct of the study. In addition, Dr. Schalper has a patent (Prediction of Response to Immune-Modulatory Therapies) issued. Dr. Skoulidis reports nonfinancial support from Tango Therapeutics Inc., outside the submitted work. Dr. Reck reports personal fees from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, MSD, Novartis, Pfizer, and Roche, outside the submitted work. Dr. Scagliotti reports personal fees from AstraZeneca, Roche, and MSD during the conduct of the study; and personal fees from Eli Lilly, Takeda, and Pfizer, outside the submitted work. The remaining authors declare no conflict of interest. Publisher Copyright: © 2020 International Association for the Study of Lung Cancer
PY - 2020/6
Y1 - 2020/6
N2 - In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies. The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti–programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents. The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies. In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities.
AB - In the past 10 years, a deeper understanding of the immune landscape of cancers, including immune evasion processes, has allowed the development of a new class of agents. The reactivation of host antitumor immune response offers the potential for long-term survival benefit in a portion of patients with thoracic malignancies. The advent of programmed cell death protein 1/programmed death ligand-1 immune checkpoint inhibitors (ICIs), both as single agents and in combination with chemotherapy, and more recently, the combination of ICI, anti–programmed cell death protein 1, and anticytotoxic T-lymphocyte antigen 4 antibody, have led to breakthrough therapeutic advances for patients with advanced NSCLC, and to a lesser extent, patients with SCLC. Encouraging activity has recently emerged in pretreated patients with thymic carcinoma (TC). Conversely, in malignant pleural mesothelioma, pivotal positive signs of activity have not been fully confirmed in randomized trials. The additive effects of chemoradiation and immunotherapy suggested intriguing potential for therapeutic synergy with combination strategies. This has led to the introduction of ICI consolidation therapy in stage III NSCLC, creating a platform for future therapeutic developments in earlier-stage disease. Despite the definitive clinical benefit observed with ICI, primary and acquired resistance represent well-known biological phenomena, which may affect the therapeutic efficacy of these agents. The development of innovative strategies to overcome ICI resistance, standardization of new patterns of ICI progression, identification of predictive biomarkers of response, optimal treatment duration, and characterization of ICI efficacy in special populations, represent crucial issues to be adequately addressed, with the aim of improving the therapeutic benefit of ICI in patients with thoracic malignancies. In this article, an international panel of experts in the field of thoracic malignancies discussed these topics, evaluating currently available scientific evidence, with the final aim of providing clinical recommendations, which may guide oncologists in their current practice and elucidate future treatment strategies and research priorities.
KW - Biomarkers
KW - Consensus
KW - Immune checkpoint inhibitors
KW - Microbiome
KW - Non–small cell lung cancer
KW - Small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85083154483&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083154483&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2020.03.006
DO - 10.1016/j.jtho.2020.03.006
M3 - Review article
C2 - 32179179
AN - SCOPUS:85083154483
SN - 1556-0864
VL - 15
SP - 914
EP - 947
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 6
ER -