title: Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma.
abstract: OBJECTIVE
  Everolimus has demonstrated its efficacy in metastatic renal cell carcinoma (mRCC). Preliminary studies have shown high variability of everolimus blood concentrations (EBC). In other settings, its activity was correlated with EBC. We therefore decided to monitor EBC in patients treated with mRCC to assess its influence on oncologic outcomes.
  
  
  METHODS
  Our study analyzed first 3 months' trough EBC levels in 42 patients treated in 4 French oncologic centers between March 2010 and August 2013. Patients presented a histologically confirmed diagnosis of mRCC and have failed prior anti-angiogenic (AA) therapies.
  
  
  RESULTS
  Median follow-up was 25.9 months. A total of 113 EBC were analyzed. The median trough concentration was 14.1 μg/L (range 2.6-91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 μg/L were free from progression at 6 months (p = 0.06). Median progression-free survival was 13.3 versus 3.9 months (HR 0.66 95 % CI 0.33-1.31; p = 0.23), and the median overall survival was 26.2 versus 9.9 months (HR 0.62 95 % CI 0.28-1.37; p = 0.24), for patients above or below the median value of trough concentrations, respectively.
  
  
  CONCLUSIONS
  Impact of drug exposure for AA tyrosine kinase inhibitors activity has been demonstrated in mRCC setting. Interpatients EBC variability was confirmed in the present study, and the results suggest a relationship between initial EBC within the first 3 months and the drug activity. It underlines the need to prospectively include EBC monitoring in future clinical trials to determine the need of its implementation in routine use.
authors.affiliation: Department of Oncology, CHU Besançon, 25030, Besançon Cedex, France, a.thieryvuillemin@mac.com.
authors.forename: A
authors.initials: A
authors.lastname: Thiery-Vuillemin
authors.forename: G
authors.initials: G
authors.lastname: Mouillet
authors.forename: T
authors.initials: T
authors.lastname: Nguyen Tan Hon
authors.forename: P
authors.initials: P
authors.lastname: Montcuquet
authors.forename: T
authors.initials: T
authors.lastname: Maurina
authors.forename: H
authors.initials: H
authors.lastname: Almotlak
authors.forename: U
authors.initials: U
authors.lastname: Stein
authors.forename: D
authors.initials: D
authors.lastname: Montange
authors.forename: A
authors.initials: A
authors.lastname: Foubert
authors.forename: V
authors.initials: V
authors.lastname: Nerich
authors.forename: X
authors.initials: X
authors.lastname: Pivot
authors.forename: B
authors.initials: B
authors.lastname: Royer
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D015331:Cohort Studies; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus