title: PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer.
abstract: The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC.
  
  
  
  Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy.
  
  
  
  Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy.
  
  
  
  PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: M-S
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Department of Biostatistics and Epidemiology and Ligue National Contre le Cancer Meta-analysis Platform, Gustave Roussy, Villejuif, France.|U1018 INSERM, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: G
authors.initials: G
authors.lastname: Le Teuff
authors.affiliation: Division of Medical Oncology and Hematology, University Health Network, Princess, Margaret, Cancer Centre, Toronto, Ontario, Canada.|Department of Medicine, University of Toronto, Toronto, Canada.
authors.forename: F A
authors.initials: FA
authors.lastname: Shepherd
authors.affiliation: Department of Biostatistics and Epidemiology and Ligue National Contre le Cancer Meta-analysis Platform, Gustave Roussy, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Landais
authors.affiliation: Institute of Advanced Biosciences, INSERM U1029, University Grenoble Alpes (UGA), Grenoble, France.
authors.forename: P
authors.initials: P
authors.lastname: Hainaut
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Filipits
authors.affiliation: Department of Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Pirker
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: T
authors.initials: T
authors.lastname: Le Chevalier
authors.affiliation: SUNY Upstate Medical University, Syracuse, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Graziano
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kratze
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: J-C
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Department of Biostatistics and Epidemiology and Ligue National Contre le Cancer Meta-analysis Platform, Gustave Roussy, Villejuif, France.|U1018 INSERM, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Pignon
authors.affiliation: Canadian Cancer Trials Group Queens University, Kingston, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Seymour
authors.affiliation: Institute of Advanced Biosciences, INSERM U1029, University Grenoble Alpes (UGA), Grenoble, France.|Department of Pathology, DACP, Centre Hospitalier Universitaire, CHUGA Grenoble, France.
authors.forename: E
authors.initials: E
authors.lastname: Brambilla
mesh_terms: D060890:B7-H1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: E1L3N antibody; LACE-Bio; PD-L1; checkpoint inhibitors; immune cells; immunotherapy