title: Correlation of PD-L1 tumor expression and treatment outcomes in patients with renal cell carcinoma receiving sunitinib or pazopanib: results from COMPARZ, a randomized controlled trial.
abstract: OBJECTIVE
  The interaction of programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving VEGF-targeted therapy.
  
  
  METHODS
  Formalin-fixed paraffin-embedded specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by IHC was evaluated using H-score (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test.
  
  
  RESULTS
  HS data were available from 453 of 1,110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS = 0). Patients with HS > 55 (n = 59, 13%) had significantly shorter overall survival (OS) than those with HS ≤ 55 in both pazopanib and sunitinib arms (median 15.1 vs. 35.6 and 15.3 vs. 27.8 months, respectively, P = 0.03). In both arms, median OS was shortest in patients with HS > 55 and intratumor CD8-positive T-cell counts > 300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS ≤ 55 and CD8-positive T-cell counts ≤ 300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results.
  
  
  CONCLUSIONS
  Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in patients with metastatic RCC receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC.
authors.affiliation: Kidney Cancer Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. toni_choueiri@dfci.harvard.edu.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: David J
authors.initials: DJ
authors.lastname: Figueroa
authors.affiliation: Kidney Cancer Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: André P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: Kidney Cancer Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Robert
authors.initials: R
authors.lastname: Gagnon
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Keith
authors.initials: K
authors.lastname: Deen
authors.affiliation: GlaxoSmithKline, Collegeville, Pennsylvania.
authors.forename: Christopher
authors.initials: C
authors.lastname: Carpenter
authors.affiliation: MEDTOX Laboratories, St. Paul, Minnesota.
authors.forename: Peter
authors.initials: P
authors.lastname: Benson
authors.affiliation: Mayo Clinic Arizona, Scottsdale, Arizona.
authors.forename: Thai H
authors.initials: TH
authors.lastname: Ho
authors.affiliation: GlaxoSmithKline, Research Triangle Park, North Carolina.
authors.forename: Lini
authors.initials: L
authors.lastname: Pandite
authors.affiliation: University of Western Sydney, Ingham Institute, Liverpool, NSW, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: de Souza
authors.affiliation: Barts Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007191:Indazoles; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D000077210:Sunitinib
chemical_list: D060890:B7-H1 Antigen; D007191:Indazoles; D007211:Indoles; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C516667:pazopanib; D000077210:Sunitinib