Increase in cholesterol predicts survival advantage in renal cell carcinoma patients treated with temsirolimus Clinical Cancer Research, 04/04/2012

Lee CK et al. – Cholesterol increase is a potential predictor for temsirolimus efficacy. Longer survival in patients treated with temsirolimus was observed in those with larger increases in cholesterol. Prospectively designed biomarker studies of mTOR inhibitors are recommended.

• The authors examined serial measurements of cholesterol, triglycerides, and glucose from patients randomized to interferon or temsirolimus in the Global Advanced Renal Cell Carcinoma Trial.
• Using time-dependent proportional-hazards models, they quantified the association between changes in these biomarkers from baseline with overall survival (OS) and progression-free (PFS).
• They also assess the extent to which changes of these biomarkers predict the effects of temsirolimus on survival.

• Temsirolimus was associated with larger mean increases in cholesterol (1.02 mmol/L; P<.0001), triglycerides (0.32mmol/L; P=.0008) and glucose (1.28mmol/L; P<.0001) compared with interferon, and improved survival (OS: HR 0.76, P=.02; PFS: HR 0.70; P=.001).
• Cholesterol increase during study was associated with longer survival (OS: hazard ratio (HR) 0.77 per mmol/L, P<.0001; PFS HR 0.81 per mmol/L; P<.0001).
• Temsirolimus effect on cholesterol, predicted its effect on survival with no additional survival advantage observed after adjusting for cholesterol change during study (OS: HR 1.14, P=.37; PFS HR 0.88, P=.35).
• Temsirolimus effect on triglycerides or glucose, did not predict its effect on survival, with survival advantage in favor of temsirolimus still observed after adjusting for these factors (p=0.003 and p=0.002).