Predictive Performance of Four Programmed Cell Death Ligand 1 Assay Systems on Nivolumab Response in Previously Treated Patients with Non-Small Cell Lung Cancer

J Thorac Oncol. 2018 Mar;13(3):377-386. doi: 10.1016/j.jtho.2017.11.123. Epub 2017 Dec 9.


Introduction: Nivolumab has demonstrated efficacy against metastatic NSCLC. Four programmed cell death ligand 1 (PD-L1) immunohistochemistry (IHC) assay systems are available for identification of responders among patients with NSCLC, and these assays show some differing characteristics. Accordingly, in this study, we evaluated the ability of these assays to identify responders to nivolumab therapy.

Methods: We retrospectively analyzed patients with previously treated advanced NSCLC, who received nivolumab between January 2016 and September 2016. Specimens were stained using four PD-L1 IHC assays (28-8, 22C3, SP142, and SP263). We classified patients as having test results that were strongly positive (tumor proportion score [TPS] ≥50%), weakly positive (TPS 1%-49%), or negative (TPS <1%).

Results: A total of 40 patients with NSCLC and their specimens were analyzed. Analytical comparisons demonstrated good concordance of PD-L1-stained tumor cells among the 28-8, 22C3, and SP263 assays (weighted κ coefficient 0.64-0.71), whereas the SP142 assay showed lower concordance with other assays (weighted κ coefficient 0.39-0.55). Progression-free survival in patients showing strongly positive PD-L1 staining classified by 28-8, 22C3, and SP263 assays was significantly longer than that in patients with a negative result for PD-L1 staining. Predictive performance of response to nivolumab, as assessed by receiver operating characteristic analysis, was also equivalent among the 28-8, 22C3, and SP263 assays (area under the curve 0.75-0.82), whereas the SP142 assay exhibited lower predictive performance (area under the curve 0.68).

Conclusions: The 28-8, 22C3, and SP263 PD-L1 IHC assays showed equivalent predictive performance, whereas the SP142 assay showed lower predictive performance.

Keywords: harmonization; immunohistochemistry; nivolumab; programmed cell death 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Death
  • Humans
  • Immunohistochemistry / methods*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Nivolumab / pharmacology
  • Nivolumab / therapeutic use*
  • Retrospective Studies


  • Antineoplastic Agents, Immunological
  • Nivolumab