BETHESDA, Maryland—The National Cancer Institute (NCI) has rejected funding for the proposed P-4 clinical trial in which researchers planned to compare raloxifene(Drug information on raloxifene) (Evista) and letrozole(Drug information on letrozole) (Femara) as breast cancer prevention agents. A letter to officials of the National Surgical Adjuvant Breast and Bowel Project (NSABP) said that "after much deliberation," NCI director John E. Niederhuber, MD, had concluded "that the numerous scientific concerns about the P-4 trial are sufficiently formidable that the NCI will not commit to the funding of this particular trial."
NCI acted 5 days after the National Cancer Advisory Board (NCAB) accepted the report of a working group of its clinical investigations subcommittee that raised significant issues about the trial. Because of cost and other issues confronting the study, "we cannot offer a strong endorsement of this trial," said Bruce A. Chabner, MD, clinical director of the Massachusetts General Hospital Cancer Center, who presented the working group's report to the advisory board.
NSABP envisioned P-4 as a logical extension of previous prevention trials showing positive results with tamoxifen(Drug information on tamoxifen) and raloxifene, but the working group pointed out that "despite their ability to decrease the number of tumors by 50%, neither has been widely adopted, probably because of concerns about side effects and the relatively low risk [of developing breast cancer] for a major segment of the female population of interest."
Dr. Chabner told the NCAB: "While the P-4 trial is a well-designed, interesting, and relevant clinical trial, even if positive, we were concerned that it is unlikely to change the practice of clinical oncology."
The P-4 study would have enrolled 12,800 postmenopausal women with a Gail score greater than 1.66 for the 5-year risk of breast cancer. Accrual was to take 4 years, with patients receiving 5 years of treatment, then 3 years of follow-up. The trial's first 5 years would have cost an estimated $54 million.
