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Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups
BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clini...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350096/ https://www.ncbi.nlm.nih.gov/pubmed/34430351 http://dx.doi.org/10.21037/tlcr-21-52 |
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author | Passiglia, Francesco Galvano, Antonio Gristina, Valerio Barraco, Nadia Castiglia, Marta Perez, Alessandro La Mantia, Maria Russo, Antonio Bazan, Viviana |
author_facet | Passiglia, Francesco Galvano, Antonio Gristina, Valerio Barraco, Nadia Castiglia, Marta Perez, Alessandro La Mantia, Maria Russo, Antonio Bazan, Viviana |
author_sort | Passiglia, Francesco |
collection | PubMed |
description | BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. METHODS: We performed a systematic review and finally included eleven first-line randomized controlled trials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standard platinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), treatment-related adverse events (TRAEs), and discontinuation rates were obtained. RESULTS: Our results demonstrated that among the different IO-based strategies (single-agent IO, Combo-IO, IO + CT) the IO + CT approach resulted in a significant increase of the ORR, albeit with no relevant improvement of survival in patients with PD-L1 ≥50%. As regards patients with negative PD-L1 expression, no significant differences in terms of activity and efficacy profile have been detected between the IO + CT and the dual checkpoint blockade. Of note, in the PD-L1 1–49% subgroup, the use of anti-PD-1 agents in association with CT led to a statistically significant gain in OS. As concerns safety, the dual checkpoint blockade seemed to be better tolerated than IO + CT. CONCLUSIONS: This meta-analysis suggested the current limited role of PD-1/CTLA-4 inhibitors combination in PD-L1-high and/or -low advanced NSCLC patients while emerging as a potentially effective and tolerable option in particular PD-L1 negative subgroups. |
format | Online Article Text |
id | pubmed-8350096 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-83500962021-08-23 Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups Passiglia, Francesco Galvano, Antonio Gristina, Valerio Barraco, Nadia Castiglia, Marta Perez, Alessandro La Mantia, Maria Russo, Antonio Bazan, Viviana Transl Lung Cancer Res Original Article BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. METHODS: We performed a systematic review and finally included eleven first-line randomized controlled trials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standard platinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), overall survival (OS), objective response rates (ORR), treatment-related adverse events (TRAEs), and discontinuation rates were obtained. RESULTS: Our results demonstrated that among the different IO-based strategies (single-agent IO, Combo-IO, IO + CT) the IO + CT approach resulted in a significant increase of the ORR, albeit with no relevant improvement of survival in patients with PD-L1 ≥50%. As regards patients with negative PD-L1 expression, no significant differences in terms of activity and efficacy profile have been detected between the IO + CT and the dual checkpoint blockade. Of note, in the PD-L1 1–49% subgroup, the use of anti-PD-1 agents in association with CT led to a statistically significant gain in OS. As concerns safety, the dual checkpoint blockade seemed to be better tolerated than IO + CT. CONCLUSIONS: This meta-analysis suggested the current limited role of PD-1/CTLA-4 inhibitors combination in PD-L1-high and/or -low advanced NSCLC patients while emerging as a potentially effective and tolerable option in particular PD-L1 negative subgroups. AME Publishing Company 2021-07 /pmc/articles/PMC8350096/ /pubmed/34430351 http://dx.doi.org/10.21037/tlcr-21-52 Text en 2021 Translational Lung Cancer Research. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Passiglia, Francesco Galvano, Antonio Gristina, Valerio Barraco, Nadia Castiglia, Marta Perez, Alessandro La Mantia, Maria Russo, Antonio Bazan, Viviana Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups |
title | Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups |
title_full | Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups |
title_fullStr | Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups |
title_full_unstemmed | Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups |
title_short | Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—a trial-level meta-analysis in PD-L1 selected subgroups |
title_sort | is there any place for pd-1/ctla-4 inhibitors combination in the first-line treatment of advanced nsclc?—a trial-level meta-analysis in pd-l1 selected subgroups |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350096/ https://www.ncbi.nlm.nih.gov/pubmed/34430351 http://dx.doi.org/10.21037/tlcr-21-52 |
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