Aggregated trial data does not indicate increased cancer risk with ezetimibe

Analysis of data from three trials involving ezetimibe does not support an association with increased risk of cancer.

Results from the SEAS trial of simvastatin plus ezetimibe suggested the possibility of an increased risk of cancer associated with ezetimibe use. Analyses of data from previous lipid lowering trials involving over 90,000 participants found no association between lipid lowering with a statin alone, and the results from SEAS include data from only a few people (101 people and 65 cancers). This paper reports further analysis with a larger dataset including cancer data from two further ongoing trials that include ezetimibe. Agreement to unblind cancer data only was obtained from independent data monitoring committees for the SHARP and IMPROVE-IT studies: these were compared with the data from SEAS. Analysis was restricted to patient with cancers recorded as having onset after starting treatment.

SHARP includes 9,264 patients, and at the point of analysis had a mean follow-up of 2.7 years; IMPROVE-IT currently includes 11,353 patients with a mean follow-up of 1.0 year. When data from the two studies were combined, there was no overall excess of cancer (313 active-treatment vs. 326 control; risk ratio, 0.96; 95% confidence interval, 0.82 to 1.12; P=0.61) and no significant excess at any particular site.

In patients receiving ezetimibe, there was a numerical excess of deaths due to cancer, but the numbers were small and the difference not statistically significant (97, vs. 72 in the control group; P=0.07), however there were fewer other cancers in the ezetimibe group compared to control – also not statistically significant (216, vs. 254 in the control group; P=0.08).

On this analysis, the authors conclude that the data do not provide any credible evidence that ezetimibe has any adverse effects on the rates of cancer. As a result, the two trials will continue until their planned finish dates, with regular interim analysis of safety data.

New Engl J Med, published early online 2 September 2008; doi: 10.1056/NEJMsa0806603 (link to abstract)