FDA Approval for Exemestane
- Approved for breast cancer
Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.On October 5, 2005, the U.S. Food and Drug Administration approved exemestane tablets (Aromasin®, a product of Pfizer Inc.) for adjuvant treatment of postmenopausal women with estrogen receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to exemestane for completion of a total of five consecutive years of adjuvant hormonal therapy.
Safety and efficacy were evaluated in the Intergroup Exemestane Study (IES), a double-blind, multicenter, international clinical trial in postmenopausal women with early stage breast cancer who had received two to three years of adjuvant tamoxifen. Four thousand seven hundred and twenty four patients in the intention-to-treat population were randomly assigned to either continue tamoxifen (20-30 mg/day) or switch to exemestane (25 mg/day) to complete a total of five years of adjuvant hormonal therapy.
Approval was based on an analysis of disease-free survival (DFS), defined as the time from randomization to the development of local or distant recurrence, contralateral breast cancer (cancer in the other breast), or death from any cause. After a median duration of randomized therapy of 27 months and with a median duration of follow-up of 34.5 months, DFS was significantly improved in patients who switched to exemestane compared to those who continued tamoxifen (HR=0.69, 95 percent CI: 0.58-0.82, p<0.0001).
In the hormone receptor-positive subpopulation representing about 85 percent of the trial patients, DFS was significantly improved (HR=0.65, 95 percent CI: 0.53-0.79, p=0.00001) in the exemestane arm compared to the tamoxifen arm. Overall survival was not significantly different in the two arms.
The most common adverse events on the IES that occurred more frequently on the exemestane arm included hot flashes, fatigue, arthralgia (joint pain), headache, insomnia (difficulty sleeping), increased sweating, hypertension (high blood pressure), and dizziness. Cardiac ischemic events (heart problems) occurred in 1.6 percent of patients in the exemestane arm of the IES compared to 0.6 percent of patients in the tamoxifen arm.
Changes in bone mineral density (BMD) were evaluated in a substudy of the IES and in a supporting safety study (027), which compared the effects of two years of exemestane to placebo. Mean decreases in BMD of the lumbar spine and femoral neck were more pronounced with exemestane than with either tamoxifen or placebo. On the IES, osteoporosis was reported in 4.6 percent of patients treated with exemestane compared to 2.8 percent of patients receiving tamoxifen.
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 "Understanding the Approval Process for New Cancer Treatments.") 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.