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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.

Original publication

DOI

10.1016/j.lungcan.2017.11.017

Type

Journal article

Journal

Lung cancer

Publication Date

01/2018

Volume

115

Pages

84 - 88

Keywords

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