PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed...

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Veröffentlicht in:Cancers 2023-11, Vol.15 (21), p.5143
Hauptverfasser: Pasqualotto, Eric, Moraes, Francisco Cezar Aquino de, Chavez, Matheus Pedrotti, Souza, Maria Eduarda Cavalcanti, Rodrigues, Anna Luíza Soares de Oliveira, Ferreira, Rafael Oliva Morgado, Lopes, Lucca Moreira, Almeida, Artur Menegaz de, Fernandes, Marianne Rodrigues, Santos, Ney Pereira Carneiro dos
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container_end_page
container_issue 21
container_start_page 5143
container_title Cancers
container_volume 15
creator Pasqualotto, Eric
Moraes, Francisco Cezar Aquino de
Chavez, Matheus Pedrotti
Souza, Maria Eduarda Cavalcanti
Rodrigues, Anna Luíza Soares de Oliveira
Ferreira, Rafael Oliva Morgado
Lopes, Lucca Moreira
Almeida, Artur Menegaz de
Fernandes, Marianne Rodrigues
Santos, Ney Pereira Carneiro dos
description Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51–0.86) and event-free survival (HR 0.53; 95% CI 0.43–0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86–10.61) and pathological complete response (OR 8.82; 95% CI 4.51–17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69–0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.
doi_str_mv 10.3390/cancers15215143
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Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51–0.86) and event-free survival (HR 0.53; 95% CI 0.43–0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86–10.61) and pathological complete response (OR 8.82; 95% CI 4.51–17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69–0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15215143</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Adjuvant treatment ; Analysis ; Apoptosis ; Bias ; Cancer ; Cancer therapies ; Care and treatment ; Cell death ; Chemotherapy ; Citation management software ; Clinical trials ; Crizotinib ; Health aspects ; Hypothyroidism ; Immunotherapy ; Kinases ; Ligands ; Lung cancer ; Lung cancer, Non-small cell ; Lung cancer, Small cell ; Lymphatic system ; Meta-analysis ; Metastases ; Metastasis ; Mortality ; Neutrophils ; Non-small cell lung carcinoma ; Patients ; PD-1 protein ; PD-L1 protein ; Small cell lung carcinoma ; Surgery ; Systematic review</subject><ispartof>Cancers, 2023-11, Vol.15 (21), p.5143</ispartof><rights>COPYRIGHT 2023 MDPI AG</rights><rights>2023 by the authors. 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/). 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Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69–0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.</description><subject>Adjuvant treatment</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Bias</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Cell death</subject><subject>Chemotherapy</subject><subject>Citation management software</subject><subject>Clinical trials</subject><subject>Crizotinib</subject><subject>Health aspects</subject><subject>Hypothyroidism</subject><subject>Immunotherapy</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Lung cancer</subject><subject>Lung cancer, Non-small cell</subject><subject>Lung cancer, Small cell</subject><subject>Lymphatic system</subject><subject>Meta-analysis</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mortality</subject><subject>Neutrophils</subject><subject>Non-small cell lung carcinoma</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Small cell lung carcinoma</subject><subject>Surgery</subject><subject>Systematic 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death</topic><topic>Chemotherapy</topic><topic>Citation management software</topic><topic>Clinical trials</topic><topic>Crizotinib</topic><topic>Health aspects</topic><topic>Hypothyroidism</topic><topic>Immunotherapy</topic><topic>Kinases</topic><topic>Ligands</topic><topic>Lung cancer</topic><topic>Lung cancer, Non-small cell</topic><topic>Lung cancer, Small cell</topic><topic>Lymphatic system</topic><topic>Meta-analysis</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Mortality</topic><topic>Neutrophils</topic><topic>Non-small cell lung carcinoma</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Small cell lung carcinoma</topic><topic>Surgery</topic><topic>Systematic review</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pasqualotto, Eric</creatorcontrib><creatorcontrib>Moraes, Francisco Cezar Aquino de</creatorcontrib><creatorcontrib>Chavez, Matheus 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Trials</atitle><jtitle>Cancers</jtitle><date>2023-11-01</date><risdate>2023</risdate><volume>15</volume><issue>21</issue><spage>5143</spage><pages>5143-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51–0.86) and event-free survival (HR 0.53; 95% CI 0.43–0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86–10.61) and pathological complete response (OR 8.82; 95% CI 4.51–17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69–0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. 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subjects Adjuvant treatment
Analysis
Apoptosis
Bias
Cancer
Cancer therapies
Care and treatment
Cell death
Chemotherapy
Citation management software
Clinical trials
Crizotinib
Health aspects
Hypothyroidism
Immunotherapy
Kinases
Ligands
Lung cancer
Lung cancer, Non-small cell
Lung cancer, Small cell
Lymphatic system
Meta-analysis
Metastases
Metastasis
Mortality
Neutrophils
Non-small cell lung carcinoma
Patients
PD-1 protein
PD-L1 protein
Small cell lung carcinoma
Surgery
Systematic review
title PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
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