title: Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors.
abstract: OBJECTIVE
  To evaluate if diastolic blood pressure (dBP) ≥90 mm Hg during axitinib treatment is a marker of efficacy.
  
  
  METHODS
  The relationship between dBP ≥90 mm Hg and efficacy was retrospectively explored across 5 phase II studies of single-agent axitinib for the treatment of 4 different tumor types. All patients had baseline BP ≤140/90 mm Hg and were stratified into 2 groups based on in-clinic BP measurements after initiating therapy: those with dBP <90 mm Hg throughout therapy and those with at least 1 dBP ≥90 mm Hg. Median overall survival (mOS), median progression-free survival (mPFS), objective response rate (ORR), and adverse events were evaluated by dBP group in individual and pooled analyses.
  
  
  RESULTS
  Two-hundred thirty patients were evaluated. Patients with dBP ≥90 mm Hg had a significantly lower relative risk of death than those with dBP <90 mm Hg [adjusted HR (95% CI) = 0.55 (0.39, 0.77); P < 0.001]. The relative risk of progression was also lower in patients with dBP ≥90 mm Hg [HR (95% CI) = 0.76 (0.54, 1.06), P = 0.107], and ORR was significantly higher (43.9% vs. 12.0%; P < 0.001). In an 8-week landmark analysis, mOS (25.8 vs. 14.9 months) and mPFS (10.2 vs. 7.1 months) were greater for patients in the ≥90 mm Hg group. Adverse events were similar between groups.
  
  
  CONCLUSIONS
  Axitinib efficacy correlated with dBP ≥90 mm Hg. Further investigation of dBP as a predictive biomarker of efficacy in patients receiving axitinib is warranted.
authors.affiliation: Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA. rinib2@ccf.org
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: John P
authors.initials: JP
authors.lastname: Fruehauf
authors.forename: Ezra E W
authors.initials: EE
authors.lastname: Cohen
authors.forename: Jamal C
authors.initials: JC
authors.lastname: Tarazi
authors.forename: Brad
authors.initials: B
authors.lastname: Rosbrook
authors.forename: Angel H
authors.initials: AH
authors.lastname: Bair
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Ricart
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Olszanski
authors.forename: Kristen J
authors.initials: KJ
authors.lastname: Letrent
authors.forename: Sinil
authors.initials: S
authors.lastname: Kim
authors.forename: Olivier
authors.initials: O
authors.lastname: Rixe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077784:Axitinib; D001794:Blood Pressure / Q000187:drug effects*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007191:Indazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D000077784:Axitinib; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3