SEAS: Increased cancer risk unlikely

Combination therapy with simvastatin and ezetimibe did not increase a patient’s risk for cancer or cancer-related death, the FDA determined after reviewing final data from the SEAS trial and preliminary results from two other studies.

FDA officials pursued an investigation following the release of preliminary SEAS results in August 2008 that indicated a possible association between increased cancer risk and death among patients who received the drug (Vytorin, Merck).

During the SEAS trial 1,873 patients with aortic stenosis were given ezetimibe 10 mg plus simvastatin 40 mg or placebo. Therapy did not lower overall CV risk after four years, the primary study endpoint, but the researchers did report higher rates of cancer in the therapy group (11.1%, n=105) vs. those in the placebo group (7.5%, n=70).

However, increases in cancer and cancer-related deaths observed in the trial may have resulted from combining many different cancer types together, the FDA wrote in a recent press release, and cancer risk among SEAS participants did not increase consistently over time with prolonged use of the therapy.

“The SEAS trial was not designed to evaluate cancer risk and the analysis of the cancer findings was not pre-specified, but rather was performed after the fact and without statistical correction to account for multiple comparisons,” the agency wrote. “Therefore, the true statistical significance of the cancer imbalance is unknown.”

The FDA also compared cancer rates among patients who participated in the SEAS trial to those participating in two ongoing trials, SHARP and IMPROVE-IT. Both are randomized trials designed to compare simvastatin plus ezetimibe therapy at different doses vs. a control. SHARP participants are assigned to 10 mg ezetimibe plus 20 mg simvastatin or placebo; IMPROVE-IT participants are assigned to 10 mg ezetimibe plus 40 mg simvastatin or 40 mg simvastatin (Zocor, Merck) alone.

After reviewing interim data from 20,617 patients from both trials, the FDA observed a nonstatistically significant increase in deaths, with 97 occurring in those who received simvastatin plus ezetimibe vs. 72 in the control groups.

“There was no consistent pattern of increased cancer risk among those being treated with [ezetimibe plus simvastatin],” the FDA wrote.

Additional data to further assess the risk for cancer among patients receiving these medications will be available once these two trials are complete. Officials expect final results from SHARP in 2010 and IMPROVE-IT in 2012.