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Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis

BACKGROUND: Although immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC), a lack of direct comparisons of various first-line treatments is clouding clinical decision-making. A network meta-analysis was conducted to compare current firs...

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Autores principales: Sheng, Lei, Gao, Jing, Xu, Qian, Zhang, Xue, Huang, Miao, Dai, Xin, Li, Song, Liu, Lian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165528/
https://www.ncbi.nlm.nih.gov/pubmed/34104227
http://dx.doi.org/10.1177/17588359211018537
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author Sheng, Lei
Gao, Jing
Xu, Qian
Zhang, Xue
Huang, Miao
Dai, Xin
Li, Song
Liu, Lian
author_facet Sheng, Lei
Gao, Jing
Xu, Qian
Zhang, Xue
Huang, Miao
Dai, Xin
Li, Song
Liu, Lian
author_sort Sheng, Lei
collection PubMed
description BACKGROUND: Although immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC), a lack of direct comparisons of various first-line treatments is clouding clinical decision-making. A network meta-analysis was conducted to compare current first-line treatments and identify the optimal regimen for patients with specific characteristics. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, Clinical Trials databases were searched from inception to 31 July 2020. Phase II/III randomized controlled trials (RCTs) comparing first-line treatments including chemotherapy, anti-angiogenesis, ICIs, and their combinations for previously untreated stage IIIB/IV or recurrent driver-gene wild-type NSCLC patients were included. RESULTS: Twenty-six RCTs were identified and included, involving 16,977 patients and a total of 18 regimens. ICI-containing treatments led to significantly prolonged overall survival (OS) compared with ICI-free treatments (0.82, 0.72–0.93). ICI plus chemotherapy had significantly longer progression-free survival (PFS; 0.70, 0.58–0.86) and marginally longer OS (0.90, 0.79–1.05) compared with ICIs alone. Ranking highest in the Bayesian network meta-analysis, pembrolizumab plus chemotherapy, nivolumab plus ipilimumab and chemotherapy, had significantly superior OS than standard chemotherapy with or without bevacizumab treatments. Pembrolizumab-chemotherapy ranked first for OS, 1-year OS rate, and subgroups of non-squamous, PD-L1 ⩾1%, non-smoking, and liver metastasis; while nivolumab–ipilimumab–chemotherapy for squamous, PD-L1 <1%, brain metastasis NSCLC. Furthermore, the ICI-containing bevacizumab-free treatments, such as pembrolizumab plus chemotherapy, nivolumab and ipilimumab with or without chemotherapy, were not significantly different from atezolizumab plus chemotherapy and bevacizumab in OS. CONCLUSIONS: A combination of ICIs with chemotherapy, rather than double ICIs, is the best first-line treatment for advanced wild-type NSCLC, with synergy that leads to better long-term survival. The panoramic view of the relative efficacy of any two regimens with different rankings provides strong evidence for selecting optimal first-line ICIs according to patients’ clinical characteristics.
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spelling pubmed-81655282021-06-07 Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis Sheng, Lei Gao, Jing Xu, Qian Zhang, Xue Huang, Miao Dai, Xin Li, Song Liu, Lian Ther Adv Med Oncol Systematic Review BACKGROUND: Although immune checkpoint inhibitors (ICIs) have improved survival for advanced wild-type non-small cell lung cancer (NSCLC), a lack of direct comparisons of various first-line treatments is clouding clinical decision-making. A network meta-analysis was conducted to compare current first-line treatments and identify the optimal regimen for patients with specific characteristics. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials, Clinical Trials databases were searched from inception to 31 July 2020. Phase II/III randomized controlled trials (RCTs) comparing first-line treatments including chemotherapy, anti-angiogenesis, ICIs, and their combinations for previously untreated stage IIIB/IV or recurrent driver-gene wild-type NSCLC patients were included. RESULTS: Twenty-six RCTs were identified and included, involving 16,977 patients and a total of 18 regimens. ICI-containing treatments led to significantly prolonged overall survival (OS) compared with ICI-free treatments (0.82, 0.72–0.93). ICI plus chemotherapy had significantly longer progression-free survival (PFS; 0.70, 0.58–0.86) and marginally longer OS (0.90, 0.79–1.05) compared with ICIs alone. Ranking highest in the Bayesian network meta-analysis, pembrolizumab plus chemotherapy, nivolumab plus ipilimumab and chemotherapy, had significantly superior OS than standard chemotherapy with or without bevacizumab treatments. Pembrolizumab-chemotherapy ranked first for OS, 1-year OS rate, and subgroups of non-squamous, PD-L1 ⩾1%, non-smoking, and liver metastasis; while nivolumab–ipilimumab–chemotherapy for squamous, PD-L1 <1%, brain metastasis NSCLC. Furthermore, the ICI-containing bevacizumab-free treatments, such as pembrolizumab plus chemotherapy, nivolumab and ipilimumab with or without chemotherapy, were not significantly different from atezolizumab plus chemotherapy and bevacizumab in OS. CONCLUSIONS: A combination of ICIs with chemotherapy, rather than double ICIs, is the best first-line treatment for advanced wild-type NSCLC, with synergy that leads to better long-term survival. The panoramic view of the relative efficacy of any two regimens with different rankings provides strong evidence for selecting optimal first-line ICIs according to patients’ clinical characteristics. SAGE Publications 2021-05-29 /pmc/articles/PMC8165528/ /pubmed/34104227 http://dx.doi.org/10.1177/17588359211018537 Text en © The Author(s), 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Systematic Review
Sheng, Lei
Gao, Jing
Xu, Qian
Zhang, Xue
Huang, Miao
Dai, Xin
Li, Song
Liu, Lian
Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis
title Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis
title_full Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis
title_fullStr Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis
title_full_unstemmed Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis
title_short Selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis
title_sort selection of optimal first-line immuno-related therapy based on specific pathological characteristics for patients with advanced driver-gene wild-type non-small cell lung cancer: a systematic review and network meta-analysis
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165528/
https://www.ncbi.nlm.nih.gov/pubmed/34104227
http://dx.doi.org/10.1177/17588359211018537
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