Exemestane Compared With Tamoxifen in Treating Postmenopausal Women With Breast Cancer

An Open Label, Randomized Multicenter Comparative Trial Of 5 Years Adjuvant Exemestane Treatment Versus 5 Years Adjuvant Tamoxifen Treatment In Postmenopausal Women With Early Breast Cancer

RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by reducing the production of estrogen. It is not yet known if exemestane is more effective than tamoxifen in preventing the recurrence of breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of exemestane with that of tamoxifen in treating postmenopausal women who have undergone surgery to remove early-stage breast cancer.

OBJECTIVES:

• Compare the efficacy and tolerability of adjuvant exemestane versus adjuvant tamoxifen in postmenopausal women with early breast cancer.
• Compare the relapse-free survival and overall survival of patients treated with these drugs.
• Compare the incidence of contralateral breast cancer in patients treated with these drugs.
• Compare the safety and long-term tolerability of these drugs in these patients.
• Compare the quality of life of patients treated with these drugs.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to estrogen receptor (ER)/progesterone receptor (PgR) status (ER positive vs ER negative/PgR positive vs ER positive/PgR unknown), prior chemotherapy (none vs taxane-based vs anthracycline-based vs other), and nodal status (negative vs 1-3 nodes positive vs 4 or more nodes positive). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral tamoxifen once daily
• Arm II: Patients receive oral exemestane once daily. Treatment in both arms continues for a minimum of 5 years in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and at months 3 and 12 during study.

Patients are followed at least annually.

PROJECTED ACCRUAL: Approximately 4,400 patients (2,200 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed early adenocarcinoma of the breast

  • Completely excised by surgery with curative intent (R0)

    • Any N OR
    • Any primary tumor greater than 3 cm OR
    • Any primary tumor grade III and greater than 1 cm

  • M0

• No positive supraclavicular nodes

• Hormone receptor status:

  • Estrogen and/or progesterone receptor positive

PATIENT CHARACTERISTICS:

Age:

• Any age
• See Menopausal status

Sex:

• Female

Menopausal status:

• Postmenopausal

  • Any age with bilateral oophorectomy or amenorrhea for at least 5 years OR

  • Age 50 or over:

    • Natural amenorrhea for at least 1 year OR
    • Chemotherapy-induced amenorrhea for at least 2 years OR
    • Radiation-induced amenorrhea (at least 3 months since prior radiotherapy) OR

  • Under age 50:

    • If amenorrheic for less than 5 years (any cause) or prior hysterectomy without bilateral surgical oophorectomy, follicle-stimulating hormone must be assayed to confirm postmenopausal status

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count greater than 100,000/mm3
• WBC greater than 3,000/mm3

Hepatic:

• SGOT or SGPT less than 2.5 times upper limit of normal (ULN)

Renal:

• Creatinine less than 1.5 times ULN

Cardiovascular:

• No uncontrolled cardiac disease
• No unstable angina
• No congestive heart failure or arrhythmia requiring medical therapy
• No myocardial infarction within the past 3 months

Other:

• No severe osteoporosis
• No other malignancies within the past 5 years except adequately treated carcinoma in situ of the cervix or basal cell skin cancer
• No other serious concurrent disease that would preclude study
• No psychiatric disorders that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior neoadjuvant chemotherapy
• No more than 10 weeks since completion of prior adjuvant chemotherapy

Endocrine therapy:

• No prior adjuvant hormonal therapy for breast cancer
• No prior neoadjuvant hormonal therapy (prior to surgery) for duration of more than 4 weeks
• At least 4 weeks since prior hormone replacement therapy

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics
• No more than 10 weeks since completion of curative surgery

Other:

• No other concurrent investigational agents or participation in another clinical study (except adjuvant cytotoxic chemotherapy studies)
• Concurrent bisphosphonates allowed