Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer – A systematic review and network meta-analysis of 3024 participants

Pui San Tan, Pedro Aguiar, Benjamin Haaland, Gilberto Lopes

Research output: Contribution to journalArticle

Abstract

Introduction Role of PD-L1 expression to guide immunotherapies in previously treated advanced NSCLC remains unclear and there is a lack of data comparing immune checkpoint inhibitors (ICIs) with each other. This network meta-analysis (NMA) aims to compare survival with ICIs to docetaxel and perform indirect comparisons between ICIs in the PD-L1 unselected population and by PD-L1 expression levels. Methods PubMed was searched and study screening was performed by two independent reviewers. NMA of survival outcomes in the PD-L1 unselected population and by PD-L1 expression levels <1%, > = 1%, > = 5%, > = 10%, and > = 50% was performed. Head-to-head indirect comparisons were constructed and treatment rankings were provided. Potential survival benefits by PD-L1 expression level as compared to a PD-L1 unselected population were estimated. Results 5 trials with 3024 total patients were included for meta-analysis. Overall, ICIs improved survival across PD-L1 expression levels compared to docetaxel, although there was only weak evidence of benefit for individual ICI nivolumab or atezolizumab in PD-L1 < 1%. PD-L1 subgroups suggested positive dose-response relationship between PD-L1 expression levels with survival benefits. In addition, there were also survival benefits due to selecting for PD-L1 in the PD-L1 > = 10% and > = 50% subgroups as compared to the PD-L1 unselected population. Indirect comparisons of ICIs showed little evidence of differences between nivolumab, pembrolizumab and atezolizumab. Discussion ICIs improve survival in previously treated advanced NSCLC patients across PD-L1 expression levels compared to docetaxel. There is a positive dose-response relationship between PD-L1 expression and survival benefits, and little evidence of survival differences between nivolumab, pembrolizumab and atezolizumab.

LanguageEnglish (US)
Pages84-88
Number of pages5
JournalLung Cancer
Volume115
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

Fingerprint

Non-Small Cell Lung Carcinoma
docetaxel
Survival
Population
Network Meta-Analysis
PubMed
Immunotherapy
Meta-Analysis
MPDL3280A
nivolumab

Keywords

  • Immune-checkpoint inhibitors
  • Meta-analysis
  • NSCLC
  • PD-L1

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer – A systematic review and network meta-analysis of 3024 participants. / Tan, Pui San; Aguiar, Pedro; Haaland, Benjamin; Lopes, Gilberto.

In: Lung Cancer, Vol. 115, 01.01.2018, p. 84-88.

Research output: Contribution to journalArticle

@article{290b7fc9540e4a36b173cab9a7b8b427,
title = "Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer – A systematic review and network meta-analysis of 3024 participants",
abstract = "Introduction Role of PD-L1 expression to guide immunotherapies in previously treated advanced NSCLC remains unclear and there is a lack of data comparing immune checkpoint inhibitors (ICIs) with each other. This network meta-analysis (NMA) aims to compare survival with ICIs to docetaxel and perform indirect comparisons between ICIs in the PD-L1 unselected population and by PD-L1 expression levels. Methods PubMed was searched and study screening was performed by two independent reviewers. NMA of survival outcomes in the PD-L1 unselected population and by PD-L1 expression levels <1{\%}, > = 1{\%}, > = 5{\%}, > = 10{\%}, and > = 50{\%} was performed. Head-to-head indirect comparisons were constructed and treatment rankings were provided. Potential survival benefits by PD-L1 expression level as compared to a PD-L1 unselected population were estimated. Results 5 trials with 3024 total patients were included for meta-analysis. Overall, ICIs improved survival across PD-L1 expression levels compared to docetaxel, although there was only weak evidence of benefit for individual ICI nivolumab or atezolizumab in PD-L1 < 1{\%}. PD-L1 subgroups suggested positive dose-response relationship between PD-L1 expression levels with survival benefits. In addition, there were also survival benefits due to selecting for PD-L1 in the PD-L1 > = 10{\%} and > = 50{\%} subgroups as compared to the PD-L1 unselected population. Indirect comparisons of ICIs showed little evidence of differences between nivolumab, pembrolizumab and atezolizumab. Discussion ICIs improve survival in previously treated advanced NSCLC patients across PD-L1 expression levels compared to docetaxel. There is a positive dose-response relationship between PD-L1 expression and survival benefits, and little evidence of survival differences between nivolumab, pembrolizumab and atezolizumab.",
keywords = "Immune-checkpoint inhibitors, Meta-analysis, NSCLC, PD-L1",
author = "Tan, {Pui San} and Pedro Aguiar and Benjamin Haaland and Gilberto Lopes",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.lungcan.2017.11.017",
language = "English (US)",
volume = "115",
pages = "84--88",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Comparative effectiveness of immune-checkpoint inhibitors for previously treated advanced non-small cell lung cancer – A systematic review and network meta-analysis of 3024 participants

AU - Tan,Pui San

AU - Aguiar,Pedro

AU - Haaland,Benjamin

AU - Lopes,Gilberto

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction Role of PD-L1 expression to guide immunotherapies in previously treated advanced NSCLC remains unclear and there is a lack of data comparing immune checkpoint inhibitors (ICIs) with each other. This network meta-analysis (NMA) aims to compare survival with ICIs to docetaxel and perform indirect comparisons between ICIs in the PD-L1 unselected population and by PD-L1 expression levels. Methods PubMed was searched and study screening was performed by two independent reviewers. NMA of survival outcomes in the PD-L1 unselected population and by PD-L1 expression levels <1%, > = 1%, > = 5%, > = 10%, and > = 50% was performed. Head-to-head indirect comparisons were constructed and treatment rankings were provided. Potential survival benefits by PD-L1 expression level as compared to a PD-L1 unselected population were estimated. Results 5 trials with 3024 total patients were included for meta-analysis. Overall, ICIs improved survival across PD-L1 expression levels compared to docetaxel, although there was only weak evidence of benefit for individual ICI nivolumab or atezolizumab in PD-L1 < 1%. PD-L1 subgroups suggested positive dose-response relationship between PD-L1 expression levels with survival benefits. In addition, there were also survival benefits due to selecting for PD-L1 in the PD-L1 > = 10% and > = 50% subgroups as compared to the PD-L1 unselected population. Indirect comparisons of ICIs showed little evidence of differences between nivolumab, pembrolizumab and atezolizumab. Discussion ICIs improve survival in previously treated advanced NSCLC patients across PD-L1 expression levels compared to docetaxel. There is a positive dose-response relationship between PD-L1 expression and survival benefits, and little evidence of survival differences between nivolumab, pembrolizumab and atezolizumab.

AB - Introduction Role of PD-L1 expression to guide immunotherapies in previously treated advanced NSCLC remains unclear and there is a lack of data comparing immune checkpoint inhibitors (ICIs) with each other. This network meta-analysis (NMA) aims to compare survival with ICIs to docetaxel and perform indirect comparisons between ICIs in the PD-L1 unselected population and by PD-L1 expression levels. Methods PubMed was searched and study screening was performed by two independent reviewers. NMA of survival outcomes in the PD-L1 unselected population and by PD-L1 expression levels <1%, > = 1%, > = 5%, > = 10%, and > = 50% was performed. Head-to-head indirect comparisons were constructed and treatment rankings were provided. Potential survival benefits by PD-L1 expression level as compared to a PD-L1 unselected population were estimated. Results 5 trials with 3024 total patients were included for meta-analysis. Overall, ICIs improved survival across PD-L1 expression levels compared to docetaxel, although there was only weak evidence of benefit for individual ICI nivolumab or atezolizumab in PD-L1 < 1%. PD-L1 subgroups suggested positive dose-response relationship between PD-L1 expression levels with survival benefits. In addition, there were also survival benefits due to selecting for PD-L1 in the PD-L1 > = 10% and > = 50% subgroups as compared to the PD-L1 unselected population. Indirect comparisons of ICIs showed little evidence of differences between nivolumab, pembrolizumab and atezolizumab. Discussion ICIs improve survival in previously treated advanced NSCLC patients across PD-L1 expression levels compared to docetaxel. There is a positive dose-response relationship between PD-L1 expression and survival benefits, and little evidence of survival differences between nivolumab, pembrolizumab and atezolizumab.

KW - Immune-checkpoint inhibitors

KW - Meta-analysis

KW - NSCLC

KW - PD-L1

UR - http://www.scopus.com/inward/record.url?scp=85035770376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85035770376&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2017.11.017

DO - 10.1016/j.lungcan.2017.11.017

M3 - Article

VL - 115

SP - 84

EP - 88

JO - Lung Cancer

T2 - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

ER -