FDA Approval for Raloxifene Hydrochloride
- Approved for breast cancer risk reduction
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.
On September 13, 2007, the U. S. Food and Drug Administration approved raloxifene hydrochloride tablets (Evista® tablets, made by Eli Lilly and Company) for reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer.
Safety and efficacy for reduction in the risk of invasive breast cancer in postmenopausal women with osteoporosis were demonstrated in three clinical trials (RUTH, MORE and CORE). The MORE (Multiple Outcomes of Raloxifene Evaluation) trial was a randomized, placebo-controlled, double-blind, multinational osteoporosis treatment study in 5,133 postmenopausal women. The effect of raloxifene hydrochloride on the incidence of breast cancer was assessed as a secondary safety endpoint. After a median of four years on treatment, raloxifene hydrochloride reduced the incidence of invasive breast cancer by 71 percent compared with placebo (HR 0.29; 95 percent CI 0.15, 0.56). There were 11 invasive breast cancers in 2,557 women on the raloxifene hydrochloride arm compared to 38 in 2,576 women on the placebo arm.
The CORE (Continuing Outcomes Relevant to Evista) trial was a follow-up study conducted in a subset of 4,011 postmenopausal women originally enrolled in the MORE trial. After a median of three additional years on treatment, raloxifene hydrochloride reduced the incidence of invasive breast cancer by 56 percent compared with placebo (HR 0.44; 99 percent CI 0.24, 0.83). There were 19 invasive breast cancers in 2,716 women on the raloxifene hydrochloride arm compared to 20 in 1,274 women on the placebo arm.
The RUTH (Raloxifene Use for the Heart) trial was a randomized, placebo-controlled, double-blind, multinational study in 10,101 postmenopausal women at increased risk of coronary events. After a median of five years on treatment, raloxifene hydrochloride reduced the incidence of invasive breast cancer by 44 percent compared with placebo (HR 0.56; 95 percent CI 0.38, 0.83). There were 40 invasive breast cancers in 5,044 women on the raloxifene hydrochloride arm compared to 70 in 5,057 women on the placebo arm.
In the MORE, CORE, and RUTH trials, the reduction in incidence of breast cancer was primarily due to a reduction in the incidence of ER-positive invasive breast cancers. There was no reduction in ER-negative invasive breast cancers, and there was no difference in incidence of noninvasive breast cancers between the raloxifene hydrochloride and placebo groups. Most invasive breast cancers were stage I or II. The number of women required to be treated for one year to prevent an invasive breast cancer in one woman ranged from 323 to 862 in the three trials.
Safety and efficacy for reduction in the risk of invasive breast cancer in postmenopausal women at high risk of breast cancer were evaluated in the STAR (Study of Tamoxifen and Raloxifene) trial. The effects of raloxifene hydrochloride 60 mg/day versus tamoxifen 20 mg/day over five years on reducing the incidence of invasive breast cancer were assessed in 19,747 postmenopausal women in a randomized, double-blind trial. Raloxifene hydrochloride was not superior to tamoxifen in reducing the incidence of invasive breast cancer. The observed incidence rates of invasive breast cancer were raloxifene hydrochloride 4.4 and tamoxifen 4.3 per 1000 women per year (risk ratio 1.02; 95 percent CI 0.82, 1.27). The results from a non-inferiority analysis are consistent with raloxifene hydrochloride potentially losing up to 35 percent of the tamoxifen effect on reduction of invasive breast cancer. Fewer noninvasive breast cancers occurred in the tamoxifen group compared to the raloxifene hydrochloride group. Raloxifene hydrochloride had a lower incidence of deep vein thrombosis, pulmonary embolism, cataract surgery and hysterectomy than tamoxifen and there was a trend for a lower incidence of endometrial cancer.
Raloxifene hydrochloride is associated with an increased risk of deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis. An increased risk of death due to stroke was observed in a trial in postmenopausal women with documented coronary heart disease or at increased risk for major coronary events. Other adverse reactions (greater than two percent and more common than with placebo) include hot flashes, leg cramps, peripheral edema, flu syndrome, arthralgia, and sweating. Each individual postmenopausal woman's risk/benefit ratio must be carefully considered.
A Medication Guide is available from Eli Lilly and Company for raloxifene hydrochloride. Women should be aware that raloxifene hydrochloride does not completely prevent breast cancer and that regular mammograms and breast examinations are essential.
This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.
The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.