Association between PD-L1 status and immune checkpoint inhibitor response in advanced malignancies: a systematic review and meta-analysis of overall survival data

Christopher J.D. Wallis, Keith Lawson, Mohit Butaney, Raj Satkunasivam, Jigarkumar Rasiklal Parikh, Stephen J. Freedland, Sandip P. Patel, Omid Hamid, Sumanta K. Pal, Zachary Klaassen

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

BACKGROUND: Targeting the programmed death ligand 1 (PD-L1) pathway has become standard for many advanced malignancies. Whether PD-L1 expression predicts response is unclear. We assessed the association between PD-L1 expression and immunotherapy response using stratified meta-analysis. METHODS: We performed a systematic review of randomized clinical trials published prior to October 2018 comparing overall survival (OS) in patients with advanced solid organ malignancies treated with immunotherapy or standard treatment. Pooled hazard ratios were calculated among patients with high and low PD-L1 levels independently. Differences between the two estimates were assessed using meta-analysis of study-level differences. Our primary analysis assessed a 1% threshold while secondary analyses utilized 5, 10 and 50%. RESULTS: 14 eligible trials reporting on 8887 patients were included. While there was a significant OS benefit for immunotherapy compared with standard treatment for all patients, the magnitude of benefit was significantly larger among those with high PD-L1 expression (P = 0.006). This finding persisted regardless of threshold used and across subgroup analyses according to PD-L1 assay type, tumor histology, line of therapy, type of inhibitor and study methodology. CONCLUSIONS: PD-L1 levels have important predictive value in determining the response to immunotherapy. However, patients with low PD-L1 levels also experience improved survival with immunotherapy compared with standard treatment.

Original languageEnglish (US)
Pages (from-to)800-809
Number of pages10
JournalJapanese Journal of Clinical Oncology
Volume50
Issue number7
DOIs
StatePublished - Jul 9 2020

Keywords

  • immunotherapy
  • medical oncology
  • PD-L1
  • PD1
  • randomized controlled trials

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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