Exemestane or Anastrozole in Treating Postmenopausal Women Who Have Undergone Surgery for Primary Breast Cancer

NCT ID: NCT00066573

Last Updated: 2023-08-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 7576 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-06
• Study Completion Date: 2012-01-06

Brief Summary

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

PURPOSE: This randomized phase III trial is studying exemestane to see how well it works compared to anastrozole in preventing cancer recurrence in postmenopausal women who have undergone surgery for primary breast cancer.

Detailed Description

OBJECTIVES:

Primary

• Compare the event-free survival of postmenopausal women with receptor-positive primary breast cancer when treated with exemestane vs anastrozole.

Secondary

• Compare the overall survival of patients treated with these regimens.
• Compare the time to distant recurrence in patients treated with these regimens.
• Compare the incidence of new primary contralateral breast cancer in patients treated with these regimens.
• Compare the incidence of all clinical fractures, specifically hip and vertebral fractures, in patients treated with these regimens.
• Compare cardiovascular morbidity and mortality (i.e., significant coronary heart disease, which includes myocardial infarctions and angina requiring percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and nonfatal strokes, and all vascular deaths) in patients treated with these regimens.
• Correlate therapy induced changes in breast density with plasma hormones and growth factors, drug levels of exemestane and anastrozole, genetic variation and breast cancer recurrence or contralateral events in patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to lymph node status at diagnosis (negative vs positive vs unknown), prior adjuvant chemotherapy (yes vs no), and herceptin use (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral exemestane (25 mg) once daily for 5 years.
• Arm II: Patients receive oral anastrozole (1 mg) once daily for 5 years. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months during the first year of study participation and annually thereafter.

PROJECTED ACCRUAL: A total of 6,840 patients will be accrued for this study.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Exemestane

Patients receive oral exemestane (25 mg) once daily for 5 years.

Group Type: EXPERIMENTAL

exemestane

Intervention Type: DRUG

Given orally

Anastrozole

Patients receive oral anastrozole (1 mg) once daily for 5 years.

Group Type: ACTIVE_COMPARATOR

anastrozole

Intervention Type: DRUG

Given orally

Interventions

anastrozole

Given orally

Intervention Type: DRUG

exemestane

Given orally

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Completely resected disease

• Primary surgery performed at least 3 weeks but no more than 3 months before study entry (if no chemotherapy was given)

• Primary surgery is defined as the last surgery at which histologic evidence of invasive or in situ disease was present in the pathology specimen
• Patients with positive sentinel lymph node biopsy are eligible provided they have had a subsequent axillary lymph node dissection
• No metachronous breast cancer
• Bilateral mammogram within the past 12 months unless initial surgery was a total mastectomy, in which case only a mammogram of the remaining breast is required
• No metastases confirmed by 1 of the following methods:

• Bone scan* (required only if alkaline phosphatase is at least 2 times normal and/or there are symptoms of metastatic disease)
• Abdominal ultrasound or CT scan (required only if AST/ALT or alkaline phosphatase is at least 2 times normal, unless the elevation is in the bone fraction)
• Chest x-ray NOTE: *Confirmatory x-ray, CT scan, or MRI required if the bone scan results are questionable
• No locally recurrent disease
• No prior or concurrent carcinoma in situ of the contralateral breast treated with partial mastectomy and/or hormonal therapy

• Patients with prior or concurrent carcinoma in situ of the ipsilateral breast are eligible provided the tumor was completely excised AND they have not received prior hormonal therapy
• Hormone receptor status:

• Estrogen receptor- and/or progesterone receptor-positive by immunohistochemistry or tumor receptor content ≥ 10 fmol/mg protein

PATIENT CHARACTERISTICS:

Age

• Postmenopausal

Sex

• Female

Menopausal status

• Postmenopausal prior to chemotherapy, defined as 1 of the following:

• Over 60 years of age
• Age 45-59 with spontaneous cessation of menses for more than 1 year prior to study entry
• Age 45-59 with menses ceasing (secondary to hysterectomy or spontaneously) within the past year AND a follicle-stimulating hormone (FSH) level prior to study entry in the postmenopausal range*
• Age 45-59, previously on hormone replacement therapy (HRT) and have discontinued HRT upon diagnosis of this malignancy AND has an FSH level prior to study entry in the postmenopausal range*
• Has undergone bilateral oophorectomy NOTE: *By institutional standards OR > 34.4 IU/L if institutional range is not available)

Performance status

• ECOG 0-2

Life expectancy

• At least 5 years

Hematopoietic

• WBC at least 3,000/mm^3 OR
• Granulocyte count at least 1,500/mm^3 AND
• Platelet count at least 100,000/mm^3

Hepatic

• See Disease Characteristics
• AST and/or ALT less than 2 times upper limit of normal (ULN)*
• Alkaline phosphatase less than 2 times ULN* NOTE: *Unless imaging examinations have ruled out metastatic disease

Renal

• Not specified

Other

• Able to swallow study medication and have adequate unassisted oral intake in order to maintain reasonable nutrition status
• No other non-breast malignancy 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 at least 5 years
• No other concurrent medical or psychiatric condition that would preclude study participation and/or interfere with results

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior and concurrent trastuzumab (Herceptin®) allowed

Chemotherapy

• See Disease Characteristics
• At least 3 weeks but no more than 3 months since prior chemotherapy
• Prior adjuvant chemotherapy allowed

Endocrine therapy

• See Disease Characteristics
• No prior aromatase inhibitor
• No prior tamoxifen or other selective estrogen receptor modulators (SERMs) except raloxifene

• At least 3 weeks since prior raloxifene
• At least 3 weeks since prior and no concurrent over-the-counter products or supplements considered to have an estrogenic effect, including any of the following:

• Ginseng
• Ginkgo biloba
• Black cohosh
• Dong quai
• Fortified soy supplements (e.g., phytoestrogen preparations)
• At least 3 weeks since other prior hormonal therapy or steroids considered to have an estrogenic effect
• No concurrent estrogens, progesterones, androgens, or SERMs

• Concurrent intermittent vaginal estrogens (e.g., vagifem, estrogen vaginal cream, testosterone, estradiol vaginal gel, or Estring) allowed if other local measures for intractable vaginal atrophy are insufficient
• No other concurrent therapy that would have an estrogenic effect, including endocrine therapy, hormonal therapy, or steroid therapy

Radiotherapy

• See Disease Characteristics
• Prior adjuvant radiotherapy allowed
• Concurrent radiotherapy allowed

Surgery

• See Disease Characteristics

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

North Central Cancer Treatment Group

NETWORK

Sponsor Role: collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul E. Goss, MD, PhD

Role: STUDY_CHAIR

Massachusetts General Hospital

James N. Ingle, MD

Role: STUDY_CHAIR

Mayo Clinic

Matthew J. Ellis, MD, PhD, FRCP

Role: STUDY_CHAIR

Washington University Siteman Cancer Center

George W. Sledge, MD

Role: STUDY_CHAIR

Indiana University Melvin and Bren Simon Cancer Center

George T. Budd, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Manuela Rabaglio, MD

Role: PRINCIPAL_INVESTIGATOR

Insel Gruppe AG, University Hospital Bern

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Lethbridge Cancer Centre

Lethbridge, Alberta, Canada

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, Canada

Penticton Regional Hospital

Penticton, British Columbia, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

The Moncton Hospital

Moncton, New Brunswick, Canada

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, Canada

Quinte Healthcare Corporation

Belleville, Ontario, Canada

Cambridge Memorial Hospital

Cambridge, Ontario, Canada

Regional Cancer Program of the Hopital Regional

Greater Sudbury, Ontario, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, Canada

Grand River Regional Cancer Centre

Kitchener, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Credit Valley Hospital

Mississauga, Ontario, Canada

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, Canada

Lakeridge Health Oshawa

Oshawa, Ontario, Canada

Algoma District Cancer Program

Sault Ste. Marie, Ontario, Canada

Niagara Health System

St. Catharines, Ontario, Canada

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Trillium Health Centre - West Toronto

Toronto, Ontario, Canada

Windsor Regional Cancer Centre

Windsor, Ontario, Canada

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, Canada

Centre de Sante et de services sociaux de Gatineau

Gatineau, Quebec, Canada

Hopital Charles LeMoyne

Greenfield Park, Quebec, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

CHA-Hopital Du St-Sacrement

Québec, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

Moy B, Elliott CR, Chapman J-AW, et al.: NCIC CTG MA.27: menopausal symptoms of ethnic minority women. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-3059, S144, 2006.

Reference Type: RESULT

Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Johnson DB, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Liedke PE, Lang I, Elliott C, Gelmon KA, Chapman JA, Shepherd LE. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013 Apr 10;31(11):1398-404. doi: 10.1200/JCO.2012.44.7805. Epub 2013 Jan 28.

Reference Type: RESULT

PMID: 23358971 (View on PubMed)

Chapman JW, Bayani J, SenGupta S, Bartlett JMS, Piper T, Quintayo MA, Virk S, Goss PE, Ingle JN, Ellis MJ, Sledge GW, Budd GT, Rabaglio M, Ansari RH, Tozer R, D'Souza DP, Chalchal H, Spadafora S, Stearns V, Perez EA, Gelmon KA, Whelan TJ, Elliott C, Shepherd LE, Chen BE, Taylor KJ. Adjunctive Statistical Standardization of Adjuvant Estrogen Receptor and Progesterone Receptor in Canadian Cancer Trials Group MA.27 Postmenopausal Breast Cancer Trial of Exemestane Versus Anastrozole. J Clin Oncol. 2024 Aug 20;42(24):2887-2898. doi: 10.1200/JCO.24.00835. Epub 2024 Jun 2.

Reference Type: DERIVED

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Ethier JL, Anderson GM, Austin PC, Clemons M, Parulekar W, Shepherd L, Summers Trasiewicz L, Tu D, Amir E. Influence of the competing risk of death on estimates of disease recurrence in trials of adjuvant endocrine therapy for early-stage breast cancer: A secondary analysis of MA.27, MA.17 and MA.17R. Eur J Cancer. 2021 May;149:117-127. doi: 10.1016/j.ejca.2021.02.034. Epub 2021 Apr 11.

Reference Type: DERIVED

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Reference Type: DERIVED

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Strasser-Weippl K, Sudan G, Ramjeesingh R, Shepherd LE, O'Shaughnessy J, Parulekar WR, Liedke PER, Chen BE, Goss PE. Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27. Eur J Cancer. 2018 Feb;90:19-25. doi: 10.1016/j.ejca.2017.11.014. Epub 2017 Dec 20.

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Reference Type: DERIVED

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Reference Type: DERIVED

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Other Identifiers

CAN-NCIC-MA27

Identifier Type: OTHER

Identifier Source: secondary_id

NCCTG-MA27

Identifier Type: OTHER

Identifier Source: secondary_id

CALGB-CAN-NCIC-MA27

Identifier Type: OTHER

Identifier Source: secondary_id

ECOG-CAN-NCIC-MA27

Identifier Type: OTHER

Identifier Source: secondary_id

SWOG-CAN-NCIC-MA27

Identifier Type: OTHER

Identifier Source: secondary_id

IBCSG-30-04

Identifier Type: OTHER

Identifier Source: secondary_id

2005-001893-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000316325

Identifier Type: OTHER

Identifier Source: secondary_id

MA27

Identifier Type: -

Identifier Source: org_study_id

NCT00438529

Identifier Type: -

Identifier Source: nct_alias