Exemestane in Preventing Cancer in Postmenopausal Women at Increased Risk of Developing Breast Cancer

A Phase III Randomized Study of Exemestane Versus Placebo in Postmenopausal Women at Increased Risk of Developing Breast Cancer

RATIONALE: The MAP.3 study was designed to test whether hormone therapy using exemestane may prevent breast cancer by blocking the production of estrogen.

PURPOSE: The study protocol was amended in May 2011 and the current purpose of the study is to allow all study participants the opportunity to complete 5 years of exemestane.

OBJECTIVES:

Primary

Previously: To determine if exemestane reduces the incidence of invasive breast cancer compared with placebo.

Currently: To determine the frequency of serious adverse events for post-menopausal women at high-risk of developing breast cancer who choose to receive 5 years of exemestane as preventative therapy.

Secondary

Previously: (same as is currently listed in PDQ) Currently: To address the Trial Committee and Sponsor's commitment to allow women who are randomized to the MAP.3 trial to receive 5 years of exemestane therapy.

OUTLINE: This study was a randomized, double-blind, placebo-controlled, multicentre study. Protocol-specified analyses were performed in April 2011. The results of these analyses are posted in the Results section. Following the amendment of May 2011, the study is now open-label and all eligible patients are receiving exemestane from participating sites for a total of 5 years. After exemestane is stopped, there is no further follow-up.

PROJECTED ACCRUAL:There were 4560 women from the United States, Canada, Spain and France who took part in this study.

• At increased risk of developing breast cancer, due to at least one of the following risk factors:

  • Gail score ≥ 1.66
  • Age ≥ 60 years
  • Prior atypical ductal hyperplasia, lobular hyperplasia, or lobular carcinoma in situ on breast biopsy
  • Prior ductal carcinoma in situ (DCIS) treated with total mastectomy with or without tamoxifen (tamoxifen must have been completed ≥ 3 months prior to randomization)

• No prior DCIS treated with lumpectomy with or without radiation

• No prior invasive breast cancer

• Not BRCA1 or BRCA2 carriers

PATIENT CHARACTERISTICS:

Previous:

• 35 and over

• Female

• Postmenopausal, defined as one of the following:

  • over 50 years of age with no spontaneous menses for at least 12 months before study entry
  • 50 years of age or under with no menses (spontaneous or secondary to hysterectomy) for at least 12 months before study entry AND with follicle-stimulating hormone level within postmenopausal range
  • Underwent prior bilateral oophorectomy

• No other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumors with no evidence of disease for ≥ 5 years

• No uncontrolled hypothyroidism or hyperthyroidism

• No major medical or psychiatric illness (including substance and alcohol abuse within the past 2 years) that would preclude study participation or compliance

• Must be accessible for treatment and follow-up

• Willing to complete quality of life questionnaires in either English or French

Current: MAP.3 participants who were randomized to the exemestane arm, are currently receiving exemestane as part of the MAP.3 study and who have not completed 5 years of exemestane.

OR MAP.3 study participants who were randomized to the placebo arm and who have either completed 5 years of study drug or who are still receiving placebo. Note: this applies only to centres that choose to allow placebo "cross-over".

PRIOR CONCURRENT THERAPY:

Previous:

• More than 3 months since prior and no concurrent hormone replacement therapies

• More than 3 months since systemic estrogenic, androgenic, or progestational agents

• More than 3 months since prior and no concurrent hormonal therapies, including, but not limited to the following:

  • Luteinizing-hormone releasing-hormone analogs (e.g., goserelin or leuprolide)
  • Progestogens (e.g., megestrol)
  • Prolactin inhibitors (e.g., bromocriptine)
  • Antiandrogens (e.g., cyproterone acetate)
  • Selective estrogen-receptor modulators (e.g., tamoxifen, toremifene, or raloxifene)

• No investigational drug within 30 days or 5 half lives prior to randomization

• No concurrent endocrine therapy

• No concurrent estrogens, androgens, or progesterones

• Concurrent low dose (≤ 100 mg/day) prophylactic aspirin allowed

• Concurrent bisphosphonates for prevention or treatment of osteoporosis allowed

• No other concurrent medications that may have an effect on study endpoints

Current: There are no prior concurrent therapy restrictions for the amended MAP.3 study.