One of the largest U.S. cancer-prevention trials ever planned has been killed after a lukewarm review. The National Cancer Institute (NCI) informed trial officials yesterday that the study, which would have tested two drugs aimed at preventing breast cancer for a cost of more than $100 million over at least 10 years, is being cancelled because of scientific concerns.
Proposed by the National Surgical Adjuvant Breast and Bowel Project (NSABP) in Pittsburgh, Pennsylvania, the STELLAR (Study to Evaluate Letrozole and Raloxifene) trial would have tested the drug letrozole against an older drug in 12,800 postmenopausal women at high risk for breast cancer. Both drugs prevent cancer by blunting the effects of estrogen, but letrozole blocks estrogen synthesis whereas the older drug blocks estrogen from stimulating tumor growth. A head-to-head comparison of the drugs would test whether letrozole works better and causes milder side effects than the older drug.
Although the trial was approved by several NCI committees, NCI Director John Niederhuber blocked it last January because of scientific questions and NCI's budget problems (ScienceNOW 13 March). At a closed meeting to review the study in March, researchers and patient groups raised several issues, including whether long-term side effects, such as a heightened risk of osteoporosis and heart attacks (two conditions estrogen protects against), would prevent letrozole from being used in clinical practice. Last week, a subcommittee of NCI's National Cancer Advisory Board stated that it could not "offer strong endorsement" for funding the trial. (See the 22 June print issue of Science for details.)
NCI has now acted on that advice. In a letter sent to NSABP and University of Pittsburgh officials yesterday, NCI officials explained that "the numerous scientific concerns ... are sufficiently formidable that the NCI will not commit to the funding of this particular trial." The letter mentions side effects and the need for better biomarkers that could help identify women at highest risk who could benefit most from participating in such a trial.
D. Lawrence Wickerham, NSABP's associate chair, told Science that the decision is "a disappointment. Clearly, we feel that this trial is scientifically important and one that has the potential to provide an option to a significant number of women." He added, "Unfortunately, we haven't been able to convince [the NCI director] that prevention is a priority."