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Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer

SIMPLE SUMMARY: The study compares the effects on complete remission rate (CR) of a single dose of durvalumab/tremelimumab immediately after a single-cycle platinum and docetaxel as part of induction therapy for a controlled trial in head and neck cancer with chemotherapy alone from a historical col...

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Autores principales: Semrau, Sabine, Gostian, Antoniu-Oreste, Traxdorf, Maximilian, Eckstein, Markus, Rutzner, Sandra, von der Grün, Jens, Illmer, Thomas, Hautmann, Matthias, Klautke, Gunther, Laban, Simon, Brunner, Thomas, Tamaskovics, Bálint, Frey, Benjamin, Zhou, Jian-Guo, Geppert, Carol-Immanuel, Hartmann, Arndt, Balermpas, Panagiotis, Budach, Wilfried, Gaipl, Udo, Iro, Heinrich, Fietkau, Rainer, Hecht, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073509/
https://www.ncbi.nlm.nih.gov/pubmed/33921668
http://dx.doi.org/10.3390/cancers13081959
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author Semrau, Sabine
Gostian, Antoniu-Oreste
Traxdorf, Maximilian
Eckstein, Markus
Rutzner, Sandra
von der Grün, Jens
Illmer, Thomas
Hautmann, Matthias
Klautke, Gunther
Laban, Simon
Brunner, Thomas
Tamaskovics, Bálint
Frey, Benjamin
Zhou, Jian-Guo
Geppert, Carol-Immanuel
Hartmann, Arndt
Balermpas, Panagiotis
Budach, Wilfried
Gaipl, Udo
Iro, Heinrich
Fietkau, Rainer
Hecht, Markus
author_facet Semrau, Sabine
Gostian, Antoniu-Oreste
Traxdorf, Maximilian
Eckstein, Markus
Rutzner, Sandra
von der Grün, Jens
Illmer, Thomas
Hautmann, Matthias
Klautke, Gunther
Laban, Simon
Brunner, Thomas
Tamaskovics, Bálint
Frey, Benjamin
Zhou, Jian-Guo
Geppert, Carol-Immanuel
Hartmann, Arndt
Balermpas, Panagiotis
Budach, Wilfried
Gaipl, Udo
Iro, Heinrich
Fietkau, Rainer
Hecht, Markus
author_sort Semrau, Sabine
collection PubMed
description SIMPLE SUMMARY: The study compares the effects on complete remission rate (CR) of a single dose of durvalumab/tremelimumab immediately after a single-cycle platinum and docetaxel as part of induction therapy for a controlled trial in head and neck cancer with chemotherapy alone from a historical collective. The CR rate was 60.3% after induction chemoimmunotherapy (ICIT; induction chemotherapy plus double immune checkpoint blockade) compared with 40.3% after induction chemotherapy (IC) alone. Patients with HPV-positive oropharyngeal cancer may benefit the most from additive double checkpoint inhibition, which is presumably due to the higher amount of infiltrating immune cells. Patients older than 60 years without HPV-positive oropharyngeal cancer are unlikely to benefit. ABSTRACT: To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m(2) d1-3 and docetaxel 75 mg/m(2) d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.
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spelling pubmed-80735092021-04-27 Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer Semrau, Sabine Gostian, Antoniu-Oreste Traxdorf, Maximilian Eckstein, Markus Rutzner, Sandra von der Grün, Jens Illmer, Thomas Hautmann, Matthias Klautke, Gunther Laban, Simon Brunner, Thomas Tamaskovics, Bálint Frey, Benjamin Zhou, Jian-Guo Geppert, Carol-Immanuel Hartmann, Arndt Balermpas, Panagiotis Budach, Wilfried Gaipl, Udo Iro, Heinrich Fietkau, Rainer Hecht, Markus Cancers (Basel) Article SIMPLE SUMMARY: The study compares the effects on complete remission rate (CR) of a single dose of durvalumab/tremelimumab immediately after a single-cycle platinum and docetaxel as part of induction therapy for a controlled trial in head and neck cancer with chemotherapy alone from a historical collective. The CR rate was 60.3% after induction chemoimmunotherapy (ICIT; induction chemotherapy plus double immune checkpoint blockade) compared with 40.3% after induction chemotherapy (IC) alone. Patients with HPV-positive oropharyngeal cancer may benefit the most from additive double checkpoint inhibition, which is presumably due to the higher amount of infiltrating immune cells. Patients older than 60 years without HPV-positive oropharyngeal cancer are unlikely to benefit. ABSTRACT: To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m(2) d1-3 and docetaxel 75 mg/m(2) d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors. MDPI 2021-04-19 /pmc/articles/PMC8073509/ /pubmed/33921668 http://dx.doi.org/10.3390/cancers13081959 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Semrau, Sabine
Gostian, Antoniu-Oreste
Traxdorf, Maximilian
Eckstein, Markus
Rutzner, Sandra
von der Grün, Jens
Illmer, Thomas
Hautmann, Matthias
Klautke, Gunther
Laban, Simon
Brunner, Thomas
Tamaskovics, Bálint
Frey, Benjamin
Zhou, Jian-Guo
Geppert, Carol-Immanuel
Hartmann, Arndt
Balermpas, Panagiotis
Budach, Wilfried
Gaipl, Udo
Iro, Heinrich
Fietkau, Rainer
Hecht, Markus
Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer
title Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer
title_full Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer
title_fullStr Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer
title_full_unstemmed Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer
title_short Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer
title_sort implementation of double immune checkpoint blockade increases response rate to induction chemotherapy in head and neck cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073509/
https://www.ncbi.nlm.nih.gov/pubmed/33921668
http://dx.doi.org/10.3390/cancers13081959
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