Impact of everolimus blood concentration on its anti-cancer activity in patients with metastatic renal cell carcinoma.
Fiche publication
Date publication
mai 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr NERICH Virginie, Pr PIVOT Xavier, Dr ROYER Bernard
Tous les auteurs :
Thiery-Vuillemin A, Mouillet G, Nguyen Tan Hon T, Montcuquet P, Maurina T, Almotlak H, Stein U, Montange D, Foubert A, Nerich V, Pivot X, Royer B
Lien Pubmed
Résumé
PURPOSE: 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. PATIENTS AND 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 mug/L (range 2.6-91.5). Fourteen patients (67 %) versus 8 (38 %) patients with median EBC above or below 14.1 mug/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. CONCLUSION: 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.
Référence
Cancer Chemother Pharmacol. 2014 May;73(5):999-1007