Effect of cholesterol and triglyceride increases on time to progression in renal clear cell cancer patients treated with everolimus.

Abstract

e15528 Background: An increased level of cholesterolemia (C) and triglyceridemia (T) secondary to an impairment of lipidic metabolism is a well known side effect of all mTOR inhibitors including everolimus. In the phase III pivotal study of everolimus in mRCC patients, an increase of C and T was reported in 77 and 73 % of patients, respectively. Increase of C and T may represent a surrogate parameter related to mTOR pathway inhibition. On these basis, we assessed the value of C and T increase as a factor predicting the efficacy of everolimus in metastatic clear cell renal cancer. Methods: We retrospectively evaluated 46 patients ( 36 male: 10 female; mean age 61.4 years +/- 11.5) with metastatic clear cell renal cancer who received a second/third line with everolimus after at least one tyrosine-kinase inhibitor (TKI). From routinely performed blood test, we retrieved the value of total C and T the day before the first everolimus admnistration and during the entire duration of treatment. We also considered for each patient variations of glycemia, blood pressure and BMI before and after beginning of treatment, as parameters of metabolic syndrome. Time to progression (TTP) and survival were evaluated. Results: Among all the potential predictive factors considered, only the increase of cholesterol and triglyceride (> 20% compared to the baseline) within 2 months from the start of everolimus correlated with efficacy. Median TTP of the 19 patients with total early C upraising was statistically significant higher than in 27 patients without upraising (14.1 months vs 5.5 months, P= 0.009). Conversely, only a positive trend favoring patients with C upraising was recorded in median survival (24.9 months vs 16.0 months, P= 0.163 ). Both median TTP and median survival were found to be statistically significant higher in the 25 patients experiencing T upraising than in the 21 patients who did not (respectively, 13.0 months vs 4.9 months, P= 0.007 and 26.4 months vs 13.4 months, P= 0.018). Conclusions: Early C and T modifications predict everolimus efficacy in renal clear cell cancer.