The complete results from a controversial study of Merck & Co and Schering-Plough’s Vytorin have done little to end claims that there is a link between the cholesterol drug and cancer.
The full report on the SEAS trial, in which 1,873 patients participated, confirmed earlier findings that Vytorin (ezetimibe/simvastatin) appears to reduce the risk of coronary artery disease events but not the rate of progression of aortic valve disease. However, it also points out that there were a total of 105 cancer cases recorded among people taking Vytorin compared with 70 taking a placebo. These figures, presented at the European Society of Cardiology meeting in Munich, are up from the 93 and 65 cases reported, respectively, in preliminary data published in July.
Presenting the data, Terje Pedersen of Ulleval University Hospital in Oslo, Norway, said that “the observed differences in cancer in the SEAS study are based on small numbers and could have occurred as a result of chance”. The data have been provided to an independent academic group for combined analysis with data from the two other large trials of simvastatin and ezetimibe, SHARP and IMPROVE-IT.
In an essay in The New England Journal of Medicine, researchers from Oxford University who are conducting that analysis said “the available results from these three trials do not provide credible evidence of any adverse effect of ezetimibe on rates of cancer”. However an NEJM editorial suggests that the debate is far from over.
It notes that “although the Oxford group may ultimately prove to be correct, it is appropriate to raise a note of caution”. The authors add that “whether the increased mortality risk is due solely to the play of chance is uncertain” and the fact that the combined data from all three trials showed an increase in cancer mortality with ezetimibe “should not be assumed to be a chance finding until further data are in”.
The editorial argues that “careful follow-up” of the patients in the SHARP and IMPROVE-IT trials “will be essential, and other existing data sets on ezetimibe-treated patients should be analysed for cancer endpoints. It concludes by saying that “physicians and patients are unfortunately left for now with uncertainty about the efficacy and safety of the drug”.
Congress wants more information
The US Congress is not impressed either. John Dingell, chairman of the Committee on Energy and Commerce, and Bart Stupak, head of the Oversight and Investigations Subcommittee, sent a letter to the CEOs of S-P and Merck to raise concerns about the latest report which “contains little more than the information that was presented at the July 21 press conference announcing the SEAS results”.
Rep Stupak said that “Vytorin’s effectiveness has been in doubt, and now its safety is questionable”.
He added that this may be another example of Merck and S-P playing with the release of a study’s data. Patients and their doctors deserve full disclosure of the study data instead of competing press releases minimizing a potentially serious safety risk.”
