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

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

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.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • B7-H1 Antigen / immunology
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Clinical Trials as Topic
  • Docetaxel / therapeutic use*
  • Humans
  • Immunotherapy / methods*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality
  • Lung Neoplasms / therapy*
  • Neoplasm Staging
  • Network Meta-Analysis
  • Survival Analysis

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • B7-H1 Antigen
  • Docetaxel