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.

Methods

  • 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.

Results

  • 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).

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