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Lung Cancer. 2018 Jan;115:84-88. doi: 10.1016/j.lungcan.2017.11.017. Epub 2017 Nov 22.

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.

Author information

1
Nuffield Department of Primary Care Health Sciences, University of Oxford, UK. Electronic address: puisan.tan@gmail.com.
2
Clinical Oncology Sector, Federal University of São Paulo, São Paulo, Brazil.
3
H. Milton Stewart School of Industrial and Systems Engineering, Georgia Institute of Technology Atlanta, USA.
4
Sylvester Comprehensive Cancer Center, University of Miami, USA.

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

PMID:
29290267
DOI:
10.1016/j.lungcan.2017.11.017
[Indexed for MEDLINE]

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