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Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis

The morbidity and mortality of lung cancer remain one of the highest among multiple cancers, respectively. Small-Cell Lung Cancer (SCLC) accounts for around 10%–15% of all lung cancers. Approximately two-thirds of the diagnosed SCLCs are in extensive stage (ES). Decades later, we still rely on the s...

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Autores principales: Abunasser, Abdulhakim A. A., Xue, Jinmin, Balawi, Ehab J. A., Zhu, Yuxi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166470/
https://www.ncbi.nlm.nih.gov/pubmed/34122547
http://dx.doi.org/10.1155/2021/6662344
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author Abunasser, Abdulhakim A. A.
Xue, Jinmin
Balawi, Ehab J. A.
Zhu, Yuxi
author_facet Abunasser, Abdulhakim A. A.
Xue, Jinmin
Balawi, Ehab J. A.
Zhu, Yuxi
author_sort Abunasser, Abdulhakim A. A.
collection PubMed
description The morbidity and mortality of lung cancer remain one of the highest among multiple cancers, respectively. Small-Cell Lung Cancer (SCLC) accounts for around 10%–15% of all lung cancers. Approximately two-thirds of the diagnosed SCLCs are in extensive stage (ES). Decades later, we still rely on the same traditional regimen with etoposide and platinum (EP) as the mainstay of treatment with poor prognosis. This meta-analysis aims to assess the effect of adding Immune Checkpoint Inhibitors (CPIs) such as (ipilimumab, atezolizumab, pembrolizumab, and durvalumab) to the traditional EP regimen for small-cell lung cancer extensive stage (ES-SCLC). We searched through PubMed looking for studies that compare between EP and CPIs, with EP alone, and only Phase III randomized controlled trials were considered eligible for this study. A total of 3645 papers were the results of the initial search, and only 4 studies met our criteria. Each investigator extracted the data independently using the PRISMA MODEL (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Each author used a prespecified sheet. The primary endpoint was to calculate OS (overall survival) and PFS (progression-free survival) hazard ratios for both arms. We found that adding EP plus CPIs increased both OS (HR, 95% CI 0.80 [0.70, 0.93], P = 0.0001, I(2) = 49%) and PFS (HR95% CI 0.81 [0.74, 0.88], P < 0.00001, I(2) = 0%). On the other hand, ORR (overall response rate) was not affected by the addition of CPIs to EP compared to EP alone, and the same was true for adverse events. To conclude, CTLA-4 alone is not encouraging, but PD-1/PD-L1 adds survival benefits. A combined treatment regimen shows to be more effective, improving overall survival rate Durvalumab and atezolizumab showed improvement for OS, but pembrolizumab and ipilimumab did not show a significant increase of OS over EP; however, pembrolizumab showed significant prolongation of the disease-free period.
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spelling pubmed-81664702021-06-11 Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis Abunasser, Abdulhakim A. A. Xue, Jinmin Balawi, Ehab J. A. Zhu, Yuxi J Oncol Research Article The morbidity and mortality of lung cancer remain one of the highest among multiple cancers, respectively. Small-Cell Lung Cancer (SCLC) accounts for around 10%–15% of all lung cancers. Approximately two-thirds of the diagnosed SCLCs are in extensive stage (ES). Decades later, we still rely on the same traditional regimen with etoposide and platinum (EP) as the mainstay of treatment with poor prognosis. This meta-analysis aims to assess the effect of adding Immune Checkpoint Inhibitors (CPIs) such as (ipilimumab, atezolizumab, pembrolizumab, and durvalumab) to the traditional EP regimen for small-cell lung cancer extensive stage (ES-SCLC). We searched through PubMed looking for studies that compare between EP and CPIs, with EP alone, and only Phase III randomized controlled trials were considered eligible for this study. A total of 3645 papers were the results of the initial search, and only 4 studies met our criteria. Each investigator extracted the data independently using the PRISMA MODEL (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Each author used a prespecified sheet. The primary endpoint was to calculate OS (overall survival) and PFS (progression-free survival) hazard ratios for both arms. We found that adding EP plus CPIs increased both OS (HR, 95% CI 0.80 [0.70, 0.93], P = 0.0001, I(2) = 49%) and PFS (HR95% CI 0.81 [0.74, 0.88], P < 0.00001, I(2) = 0%). On the other hand, ORR (overall response rate) was not affected by the addition of CPIs to EP compared to EP alone, and the same was true for adverse events. To conclude, CTLA-4 alone is not encouraging, but PD-1/PD-L1 adds survival benefits. A combined treatment regimen shows to be more effective, improving overall survival rate Durvalumab and atezolizumab showed improvement for OS, but pembrolizumab and ipilimumab did not show a significant increase of OS over EP; however, pembrolizumab showed significant prolongation of the disease-free period. Hindawi 2021-05-22 /pmc/articles/PMC8166470/ /pubmed/34122547 http://dx.doi.org/10.1155/2021/6662344 Text en Copyright © 2021 Abdulhakim A. A. Abunasser et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Abunasser, Abdulhakim A. A.
Xue, Jinmin
Balawi, Ehab J. A.
Zhu, Yuxi
Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis
title Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis
title_full Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis
title_fullStr Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis
title_full_unstemmed Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis
title_short Combination of the EP and Anti-PD-1 Pathway or Anti-CTLA-4 for the Phase III Trial of Small-Cell Lung Cancer: A Meta-Analysis
title_sort combination of the ep and anti-pd-1 pathway or anti-ctla-4 for the phase iii trial of small-cell lung cancer: a meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166470/
https://www.ncbi.nlm.nih.gov/pubmed/34122547
http://dx.doi.org/10.1155/2021/6662344
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