Letrozole in Preventing Cancer in Postmenopausal Women Who Have Received 4-6 Years of Hormone Therapy for Hormone Receptor-Positive, Lymph Node-Positive, Early-Stage Breast Cancer (SOLE)

ETOP IBCSG Partners Foundation

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: Letrozole

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00553410

2007-001370-88 (EudraCT Number)

IBCSG 35-07 / BIG 1-07

CDR0000574249 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is more effective in postmenopausal women who have received hormone therapy for early-stage breast cancer.

PURPOSE: This randomized phase III trial is comparing two different regimens of letrozole in preventing cancer in postmenopausal women who have received 4-6 years of hormone therapy for hormone receptor-positive, lymph node-positive, early-stage breast cancer.

Full description

OBJECTIVES:

Primary

• Compare the disease-free survival (DFS) of postmenopausal women treated with continuous letrozole for 5 years vs intermittent letrozole over a 5-year period.

Secondary

• Compare overall survival of patients treated with these two regimens.
• Compare distant DFS of these patients.
• Compare breast cancer-free interval of these patients.
• Compare sites of first DFS failure in these patients.
• Compare second (nonbreast) malignancies in these patients.
• Compare deaths without prior cancer events in these patients.
• Compare adverse events resulting from these two regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to treatment center and type of prior endocrine therapy (selective estrogen receptor modulators [SERMs] alone vs aromatase inhibitors [AIs] alone vs both SERMs and AIs each for at least 1 month). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral letrozole daily for 5 years.
• Arm II: Patients receive oral letrozole daily for the first 9 months of years 1 through 4, followed by 12 months in year 5.

After completion of study therapy, patients are followed annually.

Enrollment: 4,884 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of prior operable, noninflammatory breast cancer meeting the following criteria:

  • Steroid hormone receptor-positive tumors (estrogen receptor and/or progesterone receptor), determined by immunohistochemistry, after primary surgery and before commencement of prior endocrine therapy
  • Prior local treatment including surgery with or without radiotherapy for primary breast cancer with no known clinical residual loco-regional disease
  • Following primary surgery, eligible patients must have had evidence of lymph node involvement either in the axillary or internal mammary nodes, but not supraclavicular nodes
  • Clinically disease-free

• Must have completed 4-6 years of prior adjuvant selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), or a sequential combination of both

  • When calculating 4-6 years, neoadjuvant endocrine therapy should not be included

• No evidence of recurrent disease or distant metastatic disease

• No prior bilateral breast cancer

PATIENT CHARACTERISTICS:

• Female

• Must be postmenopausal by any of the following criteria:

  • Patients of any age who have had a bilateral oophorectomy (including radiation castration AND amenorrheic for > 3 months)

  • Patients 56 years old or older with any evidence of ovarian function must have biochemical evidence of definite postmenopausal status (defined as estradiol, luteinizing hormone [LH], and follicle-stimulating hormone [FSH] in the postmenopausal range)

  • Patients 55 years old or younger must have biochemical evidence of definite postmenopausal status (defined as estradiol, LH, and FSH in the postmenopausal range)

    • Patients who have received prior luteinizing-hormone releasing-hormone (LHRH) analogues within the last year are eligible if they have definite evidence of postmenopausal status as defined above

• Clinically adequate hepatic function

• No bone fracture due to osteoporosis at any time during the 4-6 years of prior therapy

• No prior or current malignancy except adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, or contra- or ipsilateral in situ breast carcinoma

• No other nonmalignant systemic diseases (cardiovascular, renal, lung, etc.) that would prevent prolonged follow-up

• No psychiatric, addictive, or any other disorder that compromises compliance with protocol requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 12 months since prior and no other concurrent endocrine SERM/AI therapy

• Any type of prior adjuvant therapy allowed including, but not limited to, any of the following:

  • Neoadjuvant chemotherapy
  • Neoadjuvant endocrine therapy
  • Adjuvant chemotherapy
  • Trastuzumab (Herceptin®)
  • Ovarian ablation
  • Gonadotropin releasing hormone analogues
  • Lapatinib ditosylate

• No concurrent hormone-replacement therapy, bisphosphonates (except for treatment of bone loss), or any other investigational agent

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4,884 participants in 2 patient groups

Continuous letrozole

Active Comparator group

Description:

Continuous letrozole: 5 years continuously (2.5 mg Letrozole daily)

Treatment:

Drug: Letrozole

Drug: Letrozole

Intermittent letrozole

Experimental group

Description:

Intermittent letrozole: 48 months over 5 yrs: 4 x 9 months (9 mo followed by 3 mo treatment-free interval in yrs 1-4, -\> 36 mo) plus 1 x 12 mo in yr 5 -\> 48 months

Treatment:

Drug: Letrozole

Drug: Letrozole