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U.S. Department of Health and Human Services

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Raloxifene hydrochloride

On September 13, 2007, the U. S. Food and Drug Administration approved raloxifene hydrochloride tablets (EVISTA, 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 trial was a randomized, placebo-controlled, double-blind, multinational osteoporosis treatment study in 5,133 postmenopausal women.  The effect of EVISTA on the incidence of breast cancer was assessed as a secondary safety endpoint.  After a median of 4 years on treatment, EVISTA reduced the incidence of invasive breast cancer by 71% compared with placebo (HR 0.29; 95% CI 0.15, 0.56).  There were 11 invasive breast cancers in 2,557 women on the EVISTA arm compared to 38 in 2,576 women on the placebo arm. 

The CORE trial was a follow-up study conducted in a subset of 4,011 postmenopausal women originally enrolled in the MORE trial.  Women were not re-randomized; the treatment assignment from the osteoporosis treatment trial was carried forward to this study.  After a median of 3 additional years on treatment, EVISTA reduced the incidence of invasive breast cancer by 56% compared with placebo (HR 0.44; 99% CI 0.24, 0.83).  There were 19 invasive breast cancers in 2,716 women on the EVISTA arm compared to 20 in 1,274 women on the placebo arm.

The RUTH 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 5 years on treatment, EVISTA reduced the incidence of invasive breast cancer by 44% compared with placebo (HR 0.56; 95% CI 0.38, 0.83).  There were 40 invasive breast cancers in 5,044 women on the EVISTA 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 EVISTA 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 trial.  The effects of EVISTA 60 mg/day versus tamoxifen 20 mg/day over 5 years on reducing the incidence of invasive breast cancer were assessed in 19,747 postmenopausal women in a randomized, double-blind trial.  EVISTA was not superior to tamoxifen in reducing the incidence of invasive breast cancer.  The observed incidence rates of invasive breast cancer were EVISTA 4.4 and tamoxifen 4.3 per 1000 women per year (risk ratio 1.02; 95% CI 0.82, 1.27).  The results from a non-inferiority analysis are consistent with EVISTA potentially losing up to 35% of the tamoxifen effect on reduction of invasive breast cancer.  Fewer noninvasive breast cancers occurred in the tamoxifen group compared to the EVISTA group.  EVISTA 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.

EVISTA 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 (>2% 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 for Evista.  Women should be aware that Evista does not completely prevent breast cancer and that regular mammograms and breast examinations are essential. 

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications, is available at Drugs@FDA.

 

FDA News: FDA Approves New Uses for Evista

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Date created: September 17, 2007