title: Five-year survival in patients with cytokine-refractory metastatic renal cell carcinoma treated with axitinib.
abstract: BACKGROUND
  In a phase II study of axitinib for cytokine-refractory metastatic renal cell carcinoma, median overall survival (OS) was 29.9 months (95% CI, 20.3 to not estimable months).
  
  
  METHODS
  Long-term survival data were collected retrospectively from 52 patients with cytokine-refractory metastatic renal cell carcinoma who received axitinib in a completed phase II study (protocol 1), 11 of whom enrolled in a continuing access protocol (protocol 2), for the current observational study (protocol 3). In a post hoc analysis, the patients were grouped into quartiles based on cycle 1 day 1, 1- to 2-hour post-dose axitinib plasma levels to explore the impact of drug exposure on efficacy.
  
  
  RESULTS
  The 5-year survival rate was 20.6% (95% CI, 10.9%-32.4%), with a median follow-up of 5.9 years. Frequent all-grade adverse events were fatigue (n = 38; 73.1%), diarrhea (n = 34; 65.4%), hypertension (n = 33; 63.5%), and nausea (n = 33; 63.5%). Quartile 3 patients (axitinib level, 45.2-56.4 ng/mL; n = 12) had the best clinical outcome: objective response rate 82%, median progression-free survival (PFS) 28.3 months, and median OS that was not reached after 5 years.
  
  
  CONCLUSIONS
  Axitinib was well tolerated and provided an estimated 5-year survival rate of 20.6% for cytokine-refractory metastatic renal cell carcinoma. Exploratory analyses showed numerically higher objective response rate and longer OS and PFS in patients who achieved post-first-dose axitinib plasma concentrations within a specific range.
authors: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 44195, USA. rinib2@ccf.org
authors: Brian I
authors: BI
authors: Rini
authors: Thibault
authors: T
authors: de La Motte Rouge
authors: Andrea L
authors: AL
authors: Harzstark
authors: M Dror
authors: MD
authors: Michaelson
authors: Glenn
authors: G
authors: Liu
authors: Viktor
authors: V
authors: Grünwald
authors: Antonella
authors: A
authors: Ingrosso
authors: Michael A
authors: MA
authors: Tortorici
authors: Paul
authors: P
authors: Bycott
authors: Sinil
authors: S
authors: Kim
authors: Joanna
authors: J
authors: Bloom
authors: Robert J
authors: RJ
authors: Motzer
mesh_terms: D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007191:Indazoles / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib