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

NCT00066573 | Completed Phase 3 Results DMC FDA Drug

• 9 other identifiers: MA27CAN-NCIC-MA27NCCTG-MA27CALGB-CAN-NCIC-MA27ECOG-CAN-NCIC-MA27SWOG-CAN-NCIC-MA27IBCSG-30-042005-001893-28CDR0000316325
• Study Type: interventional
• Target: 7,576
• Locations: 1 country
• Sites: 39

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.

Conditions

Breast Cancer

Keywords

stage IIIA breast cancer; stage I breast cancer; stage II breast cancer

Outcome Measures

Primary Outcomes (1)

• Event-free Survival

  Event free survival, the primary endpoint of this study, is defined as the time from randomization to the time of documented locoregional or distant recurrence, new primary breast cancer, or death from any cause.

  5 years

Secondary Outcomes (3)

• Overall Survival: Percentage of Participants Alive at 5 Years

  5 years

• Distant Disease-free Survival: Number of Participants Without Documented Distant Recurrence

  5 years

• Clinical Fracture Rate: Number of Participants With Bone Fractures.

  8 years

Study Arms (2)

Exemestane

EXPERIMENTAL

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

Drug: exemestane

Anastrozole

ACTIVE COMPARATOR

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

Drug: anastrozole

Interventions

anastrozole DRUG

Given orally

Anastrozole

exemestane DRUG

Given orally

Exemestane

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed invasive breast cancer * pT1-3; pNX, pN0-2 or pN3\*; M0 * Neoadjuvant patients are eligible no earlier than 3 weeks or later than 3 months after excisional surgery, provided both the clinical-diagnostic staging of cancer and postsurgical resection-pathologic staging of cancer meet the requirements for primary tumor, regional lymph nodes, and distant metastasis classification NOTE: \*Only when the sole basis for this classification is the presence of 10 or more involved axillary lymph nodes * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead
• National Cancer Institute (NCI): collaborator
• North Central Cancer Treatment Group: collaborator
• Cancer and Leukemia Group B: collaborator
• Eastern Cooperative Oncology Group: collaborator
• SWOG Cancer Research Network: collaborator
• ETOP IBCSG Partners Foundation: collaborator

Study Sites (39)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Lethbridge Cancer Centre

Lethbridge, Alberta, T1J 1W5, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

Penticton Regional Hospital

Penticton, British Columbia, V2A 3G6, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

Dr. H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, AIB 3V6, Canada

Location

Quinte Healthcare Corporation

Belleville, Ontario, K8N 5A9, Canada

Location

Cambridge Memorial Hospital

Cambridge, Ontario, N1R 3G2, Canada

Location

Regional Cancer Program of the Hopital Regional

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2R 7C6, Canada

Location

Thunder Bay Regional Health Science Centre

Thunder Bay, Ontario, P7B 6V4, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Trillium Health Centre - West Toronto

Toronto, Ontario, M9C 1A5, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

PEI Cancer Treatment Centre,Queen Elizabeth Hospital

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

Centre de Sante et de services sociaux de Gatineau

Gatineau, Quebec, J8P 7H2, Canada

Location

Hopital Charles LeMoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (9)

• 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.

  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.

  PMID: 23358971 RESULT

• 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.

  PMID: 38824432 DERIVED

• 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.

  PMID: 33853037 DERIVED

• Strasser-Weippl K, Higgins MJ, Chapman JW, Ingle JN, Sledge GW, Budd GT, Ellis MJ, Pritchard KI, Clemons MJ, Badovinac-Crnjevic T, Han L, Gelmon KA, Rabaglio M, Elliott C, Shepherd LE, Goss PE. Effects of Celecoxib and Low-dose Aspirin on Outcomes in Adjuvant Aromatase Inhibitor-Treated Patients: CCTG MA.27. J Natl Cancer Inst. 2018 Sep 1;110(9):1003-1008. doi: 10.1093/jnci/djy017.

  PMID: 29554282 DERIVED

• 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.

  PMID: 29274617 DERIVED

• Yerushalmi R, Dong B, Chapman JW, Goss PE, Pollak MN, Burnell MJ, Levine MN, Bramwell VHC, Pritchard KI, Whelan TJ, Ingle JN, Shepherd LE, Parulekar WR, Han L, Ding K, Gelmon KA. Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials. Ann Oncol. 2017 Jul 1;28(7):1560-1568. doi: 10.1093/annonc/mdx152.

  PMID: 28379421 DERIVED

• Stearns V, Chapman JA, Ma CX, Ellis MJ, Ingle JN, Pritchard KI, Budd GT, Rabaglio M, Sledge GW, Le Maitre A, Kundapur J, Liedke PE, Shepherd LE, Goss PE. Treatment-associated musculoskeletal and vasomotor symptoms and relapse-free survival in the NCIC CTG MA.27 adjuvant breast cancer aromatase inhibitor trial. J Clin Oncol. 2015 Jan 20;33(3):265-71. doi: 10.1200/JCO.2014.57.6926. Epub 2014 Dec 15.

  PMID: 25512454 DERIVED

• Goetz MP, Schaid DJ, Wickerham DL, Safgren S, Mushiroda T, Kubo M, Batzler A, Costantino JP, Vogel VG, Paik S, Carlson EE, Flockhart DA, Wolmark N, Nakamura Y, Weinshilboum RM, Ingle JN, Ames MM. Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical trials. Clin Cancer Res. 2011 Nov 1;17(21):6944-51. doi: 10.1158/1078-0432.CCR-11-0860. Epub 2011 Aug 31.

  PMID: 21880792 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Wendy Parulekar
• Organization: NCIC Clinical Trials Group

wparulekar@ctg.queensu.ca

1-613-533-6430

Study Officials

• Paul E. Goss, MD, PhD

  Massachusetts General Hospital

  STUDY CHAIR

• James N. Ingle, MD

  Mayo Clinic

  STUDY CHAIR

• Matthew J. Ellis, MD, PhD, FRCP

  Washington University Siteman Cancer Center

  STUDY CHAIR

• George W. Sledge, MD

  Indiana University Melvin and Bren Simon Cancer Center

  STUDY CHAIR

• George T. Budd, MD

  The Cleveland Clinic

  STUDY CHAIR

• Manuela Rabaglio, MD

  Insel Gruppe AG, University Hospital Bern

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2003
• First Posted: August 7, 2003
• Study Start: June 6, 2003
• Primary Completion: November 7, 2010
• Study Completion: January 6, 2012
• Last Updated: August 25, 2023
• Results First Posted: May 15, 2014

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (39)