title: Long-Term Safety With Axitinib in Previously Treated Patients With Metastatic Renal Cell Carcinoma.
abstract: BACKGROUND
  Axitinib is an approved treatment for advanced renal cell carcinoma (RCC) after failure of 1 systemic therapy.
  
  
  METHODS
  Long-term safety with single-agent axitinib was analyzed using pooled data from clinical trials in 672 previously treated patients with metastatic RCC (mRCC) and in 1304 patients with different advanced solid tumors. In all studies, except the phase I first-in-human, dose-finding study, the starting dose of oral axitinib was 5 mg twice daily continuously. Common long-term treatment-emergent adverse events (AEs) were identified in patients who received axitinib for ≥ 2 years, then evaluated in all patients, and assessed using interval, cumulative, and latency analyses.
  
  
  RESULTS
  In all, 108 (16%) previously treated patients with mRCC received axitinib for ≥ 2 years. In interval analysis, most AEs occurred during the first 6 months of treatment, with rates stable or decreased over time; rates increased for proteinuria, peripheral edema, and increased blood creatinine. Common Grade ≥ 3 AE rates declined or plateaued over time, except for increased amylase and myocardial infarction. Results were similar in cumulative analysis in this population, and in interval and cumulative analyses in all patients with mRCC and those with advanced solid tumors.
  
  
  CONCLUSIONS
  Declining or stable rates of most AEs support an acceptable long-term safety profile for axitinib in patients with mRCC. However, increases in the rates of some AEs warrant monitoring. This analysis is limited in that it was retrospective and included a relatively small patient population.
authors: Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH. Electronic address: rinib2@ccf.org.
authors: Brian I
authors: BI
authors: Rini
authors: Gustave Roussy/Medical Oncology Department, Villejuif, France.
authors: Bernard
authors: B
authors: Escudier
authors: Pfizer Oncology, New York, NY.
authors: Subramanian
authors: S
authors: Hariharan
authors: Pfizer Oncology, New York, NY.
authors: W Gregory
authors: WG
authors: Roberts
authors: Pfizer Oncology, New York, NY.
authors: Jamal
authors: J
authors: Tarazi
authors: Pfizer Oncology, New York, NY.
authors: Brad
authors: B
authors: Rosbrook
authors: Pfizer Safety Evaluation and Reporting, Peapack, NJ.
authors: Zena
authors: Z
authors: Askerova
authors: Pfizer Oncology, New York, NY.
authors: Liza L
authors: LL
authors: DeAnnuntis
authors: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
authors: Robert J
authors: RJ
authors: Motzer
mesh_terms: D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies
chemical_list: D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D000077784:Axitinib
keywords: adverse events; tyrosine kinase inhibitor; vascular endothelial growth factor receptor