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A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression
In the absence of head-to-head trials of first-line treatments for metastatic non-small cell lung cancer (NSCLC), synthesis of available evidence is needed. We conducted a systematic literature review and network meta-analysis of randomized controlled trials in patients with stage IV NSCLC and high...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300186/ https://www.ncbi.nlm.nih.gov/pubmed/34307144 http://dx.doi.org/10.3389/fonc.2021.676732 |
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author | Herbst, Roy Jassem, Jacek Abogunrin, Seye James, Daniel McCool, Rachael Belleli, Rossella Giaccone, Giuseppe De Marinis, Filippo |
author_facet | Herbst, Roy Jassem, Jacek Abogunrin, Seye James, Daniel McCool, Rachael Belleli, Rossella Giaccone, Giuseppe De Marinis, Filippo |
author_sort | Herbst, Roy |
collection | PubMed |
description | In the absence of head-to-head trials of first-line treatments for metastatic non-small cell lung cancer (NSCLC), synthesis of available evidence is needed. We conducted a systematic literature review and network meta-analysis of randomized controlled trials in patients with stage IV NSCLC and high programmed death-ligand 1 (PD-L1) expression. Patients with other-stage NSCLC or without PD-L1 expression and populations with < 80% stage IV NSCLC were excluded. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events. English records from MEDLINE and Embase published through October 2020 were eligible, supplemented by hand searches of other sources. Three evidence networks were constructed based on histology (mixed, squamous, non-squamous). OS and PFS results were analyzed applying Bayesian fractional polynomial random-effects models. Hazard ratios over time with 95% credible intervals (CrIs) and expected differences in OS and PFS between each cancer immunotherapy regimen and the chemotherapy common comparator were generated. Seventeen clinical trials were included after screening 32,527 records. Heterogeneity and risk of bias were generally low across trials. In the mixed-histology network of PD-L1–high patients, expected OS was significantly longer with atezolizumab (estimated difference: 10.4 months [95% CrI: 1.9, 18.2]), pembrolizumab (7.2 [2.2, 12.3]), and cemiplimab (13.0 [4.2, 21.0]) versus chemotherapy but not with nivolumab (3.5 [−2.5, 10.6]) or nivolumab plus ipilimumab (6.7 [−0.5, 14.2]) versus chemotherapy. OS improvements were not significant compared with chemotherapy for any regimen in the squamous and non-squamous networks, except pembrolizumab plus chemotherapy in the non-squamous network. All regimens showed significantly longer expected PFS versus chemotherapy in the non-squamous network, whereas the increases were not significant in the mixed or squamous networks. ORR was significantly higher with pembrolizumab and cemiplimab versus chemotherapy in the mixed-histology network, with sintilimab in the non-squamous network, and with combination regimens, including pembrolizumab or atezolizumab, in the squamous and non-squamous networks, except with atezolizumab plus carboplatin, paclitaxel, and bevacizumab. Survival and safety versus chemotherapy were generally similar across cancer immunotherapies and histology networks. These findings may support treatment decisions for patients with high PD-L1 status receiving first-line treatment for NSCLC. |
format | Online Article Text |
id | pubmed-8300186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83001862021-07-24 A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression Herbst, Roy Jassem, Jacek Abogunrin, Seye James, Daniel McCool, Rachael Belleli, Rossella Giaccone, Giuseppe De Marinis, Filippo Front Oncol Oncology In the absence of head-to-head trials of first-line treatments for metastatic non-small cell lung cancer (NSCLC), synthesis of available evidence is needed. We conducted a systematic literature review and network meta-analysis of randomized controlled trials in patients with stage IV NSCLC and high programmed death-ligand 1 (PD-L1) expression. Patients with other-stage NSCLC or without PD-L1 expression and populations with < 80% stage IV NSCLC were excluded. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events. English records from MEDLINE and Embase published through October 2020 were eligible, supplemented by hand searches of other sources. Three evidence networks were constructed based on histology (mixed, squamous, non-squamous). OS and PFS results were analyzed applying Bayesian fractional polynomial random-effects models. Hazard ratios over time with 95% credible intervals (CrIs) and expected differences in OS and PFS between each cancer immunotherapy regimen and the chemotherapy common comparator were generated. Seventeen clinical trials were included after screening 32,527 records. Heterogeneity and risk of bias were generally low across trials. In the mixed-histology network of PD-L1–high patients, expected OS was significantly longer with atezolizumab (estimated difference: 10.4 months [95% CrI: 1.9, 18.2]), pembrolizumab (7.2 [2.2, 12.3]), and cemiplimab (13.0 [4.2, 21.0]) versus chemotherapy but not with nivolumab (3.5 [−2.5, 10.6]) or nivolumab plus ipilimumab (6.7 [−0.5, 14.2]) versus chemotherapy. OS improvements were not significant compared with chemotherapy for any regimen in the squamous and non-squamous networks, except pembrolizumab plus chemotherapy in the non-squamous network. All regimens showed significantly longer expected PFS versus chemotherapy in the non-squamous network, whereas the increases were not significant in the mixed or squamous networks. ORR was significantly higher with pembrolizumab and cemiplimab versus chemotherapy in the mixed-histology network, with sintilimab in the non-squamous network, and with combination regimens, including pembrolizumab or atezolizumab, in the squamous and non-squamous networks, except with atezolizumab plus carboplatin, paclitaxel, and bevacizumab. Survival and safety versus chemotherapy were generally similar across cancer immunotherapies and histology networks. These findings may support treatment decisions for patients with high PD-L1 status receiving first-line treatment for NSCLC. Frontiers Media S.A. 2021-07-09 /pmc/articles/PMC8300186/ /pubmed/34307144 http://dx.doi.org/10.3389/fonc.2021.676732 Text en Copyright © 2021 Herbst, Jassem, Abogunrin, James, McCool, Belleli, Giaccone and De Marinis https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Herbst, Roy Jassem, Jacek Abogunrin, Seye James, Daniel McCool, Rachael Belleli, Rossella Giaccone, Giuseppe De Marinis, Filippo A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression |
title | A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression |
title_full | A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression |
title_fullStr | A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression |
title_full_unstemmed | A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression |
title_short | A Network Meta-Analysis of Cancer Immunotherapies Versus Chemotherapy for First-Line Treatment of Patients With Non-Small Cell Lung Cancer and High Programmed Death-Ligand 1 Expression |
title_sort | network meta-analysis of cancer immunotherapies versus chemotherapy for first-line treatment of patients with non-small cell lung cancer and high programmed death-ligand 1 expression |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300186/ https://www.ncbi.nlm.nih.gov/pubmed/34307144 http://dx.doi.org/10.3389/fonc.2021.676732 |
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