Study of Faslodex +/- Concomitant Arimidex v Exemestane Following Progression on Non-steroidal Aromatase Inhibitors (SoFEA)

A Partially Blind Phase III Randomised Trial of Faslodex +/- Concomitant Arimidex Compared With Exemestane in Post-menopausal Women With ER+ or PR+ Locally Advanced/Metastatic Breast Cancer Following Progression on Non-steroidal AIs

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant, anastrozole, or exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. It is not yet known whether giving fulvestrant together with anastrozole is more effective than giving fulvestrant together with a placebo or exemestane alone in treating breast cancer.

PURPOSE: This randomized phase III trial is studying fulvestrant and anastrozole to see how well they work compared to fulvestrant and a placebo or exemestane alone in treating postmenopausal women with locally advanced or metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Exemestane; Drug: Anastrozole

Detailed Description

OBJECTIVES:

Primary

• Compare progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive, locally advanced or metastatic breast cancer that relapsed or progressed during prior treatment with nonsteroidal aromatase inhibitors treated with fulvestrant with vs without anastrozole vs exemestane alone.

Secondary

• Compare the objective complete response (CR) and partial response (PR) rate and duration of response in patients treated with these regimens.
• Compare the clinical benefit (i.e., 6-month CR, PR, and stable disease) rate and duration of clinical benefit in patients treated with these regimens.
• Compare time to treatment failure in patients treated with these regimens.
• Compare the overall survival of patients treated with these regimens.
• Compare the tolerability of these regimens in these patients.

OUTLINE: This is a randomized, partially double-blind and placebo-controlled, multicenter study. Patients are stratified according to the setting in which prior nonsteroidal aromatase-inhibitor therapy was given (adjuvant therapy vs first-line therapy) and participating center. Patients are randomized to 1 of 3 treatment arms.

• Arm I (fulvestrant and anastrozole): Patients receive fulvestrant intramuscularly (IM) on days 1, 15, and 29 and then once monthly. Patients receive oral anastrozole once daily.
• Arm II (fulvestrant and placebo): Patients receive fulvestrant as in arm I and oral placebo once daily.
• Arm III (exemestane alone): Patients receive oral exemestane once daily. In all arms, treatment repeats every month in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for survival.

PROJECTED ACCRUAL: A total of 750 patients (250 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 698
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden - London
    • Sutton, England, United Kingdom, SM2 5NG
      • Institute of Cancer Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the breast

  • Locally advanced or metastatic disease

• Metastatic disease must be measurable or evaluable

  • Patients with bone only metastases are eligible provided there is an evaluable site of bone metastasis that can be followed by x-ray, MRI, or CT scan

• Relapsed or progressed during prior treatment with single-agent nonsteroidal aromatase inhibitor (NSAI)*, meeting either of the following criteria:

  • NSAI given as adjuvant therapy that lasted ≥ 12 months

  • Achieved an objective complete response, partial response, or stable disease that lasted ≥ 6 months after prior first-line therapy with NSAI for locally advanced or metastatic disease

    • Chemotherapy as part of the first-line therapy given before initiation of NSAI allowed NOTE: *Patients are required to continue to take NSAI until beginning of study treatment.
• No rapidly progressive visceral disease (i.e., lymphangitis carcinomatosa or diffuse hepatic involvement)

• Hormone receptor status:

  • Estrogen receptor (ER) and/or progesterone receptor positive tumor
  • No ER-unknown disease

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Postmenopausal, as defined by 1 of the following criteria:

  • Age 60 and over
  • Age 45 to 59 AND ≥ 12 months since last menstrual period with no prior hysterectomy
  • Any age with prior bilateral oophorectomy

Performance status

• WHO 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

  • No thrombocytopenia
• Hemoglobin ≥ 10 g/dL

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN (unless due to bone metastases)
• No liver disease

Renal

• Creatinine < 1.97 mg/dL

Other

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Chemotherapy

• See Disease Characteristics
• Prior neoadjuvant or adjuvant chemotherapy allowed

Endocrine therapy

• See Disease Characteristics
• Prior tamoxifen as neoadjuvant or adjuvant therapy allowed
• No systemic corticosteroids that lasted > 15 days within the past 4 weeks

Other

• More than 4 weeks since prior investigational drugs

• Concurrent bisphosphonates for bone metastases allowed provided bisphosphonate therapy has been established for ≥ 6 months

  • Concurrent initiation of bisphosphonate allowed provided patient has soft tissue or visceral metastases as the measurable or evaluable target lesion
• No concurrent anticoagulant therapy
• No concurrent unlicensed noncancer investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Faslodex + placebo; Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Placebo orally once a day	Drug: Fulvestrant; Other Names: Faslodex; Drug: Anastrozole; This may be Anastrazole OR a placebo; Other Names: Arimidex (or placebo)
Active Comparator: Faslodex + Arimidex; Arimidex/placebo comparator is blinded Faslodex (fulvestrant) IM on day 1,15,29 and monthly thereafter Arimidex (anastrozole) orally once a day	Drug: Fulvestrant; Other Names: Faslodex; Drug: Anastrozole; This may be Anastrazole OR a placebo; Other Names: Arimidex (or placebo)
Active Comparator: Exemestane; exemestane orally once a day	Drug: Exemestane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival	defined as time from randomisation to progression of existing disease, new sites of disease, second primary cancer if change in systemic treatment was necessary, or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Assessed up to 190 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The proportion of patients identified as having a complete response (CR) or partial response (PR) at any time whilst on study treatment. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a >=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Objective Response (OR) = CR + PR	From start of treatment, every 3 months to treatment discontinuation and/or up to 190 months
Duration of Response	time from first assessment of response to progression or death. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a >=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Assessed up to 190 months
Clinical Benefit Rate	Complete or partial response or stable disease for at least six months prior to progression. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a >=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Stable disease is neither responding or progressing. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Assessed up to 190 months
Duration of Clinical Benefit	Time from first assessment of clinical benefit to progression or death. Response is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as either disappearance of all lesions or a >=30% decrease in the sum of the longest diameter of target lesions with no progressing non-target lesions and no new lesions. Stable disease is neither responding or progressing. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Clinical benefit = (CR+PR)+(SD>=6months).	Assessed up to 190 months
Time to Treatment Failure	Time from randomisation to discontinuation of protocol treatment for any reason, or progression of disease	To discontinuation of protocol treatment for any reason, or progression of disease assessed up to 190 months
Overall Survival	Time from randomisation until death from any cause.	To death assessed up to 190 months.
Tolerability of Treatment	To evaluate the overall safety and tolerability. The number of patients experiencing at least one adverse event. Refer to adverse event section for more details.	From start of treatment to discontinuation of treatment/progression assessed up to 190 months

Collaborators and Investigators

• Sponsor: Institute of Cancer Research, United Kingdom
• Collaborators: Royal Marsden NHS Foundation Trust
• Investigators: Study Chair: Stephen RD Johnston, MD,PhD,FRCP, Royal Marsden NHS Foundation Trust

Publications and helpful links

General Publications

• Fribbens C, O'Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, Cristofanilli M, Andre F, Loi S, Loibl S, Jiang J, Bartlett CH, Koehler M, Dowsett M, Bliss JM, Johnston SR, Turner NC. Plasma ESR1 Mutations and the Treatment of Estrogen Receptor-Positive Advanced Breast Cancer. J Clin Oncol. 2016 Sep 1;34(25):2961-8. doi: 10.1200/JCO.2016.67.3061. Epub 2016 Jun 6.
• Johnston SR, Kilburn LS, Ellis P, Dodwell D, Cameron D, Hayward L, Im YH, Braybrooke JP, Brunt AM, Cheung KL, Jyothirmayi R, Robinson A, Wardley AM, Wheatley D, Howell A, Coombes G, Sergenson N, Sin HJ, Folkerd E, Dowsett M, Bliss JM; SoFEA investigators. Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial. Lancet Oncol. 2013 Sep;14(10):989-98. doi: 10.1016/S1470-2045(13)70322-X. Epub 2013 Jul 29.

Helpful Links

• Clinical trial summary from ICR website

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2004
• Primary Completion (Actual): November 28, 2022
• Study Completion (Actual): November 28, 2022

Study Registration Dates

• First Submitted: November 11, 2005
• First Submitted That Met QC Criteria: November 11, 2005
• First Posted (Estimated): November 15, 2005

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: stage IV breast cancer; recurrent breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Receptor Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Fulvestrant; Anastrozole; Exemestane
• Other Study ID Numbers: CDR0000448616; ICR-CTSU-SOFEA (Other Identifier: ICR-CTSU); ISRCTN44195747 (Other Identifier: ISRCTN); MREC-03677 (Other Identifier: REC); 2004-000093-30 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data, together with a data dictionary defining each field in the set, will be made available to other researchers on request, subject to the approval of a formal data access request in accordance with the ICR-CTSU data and sample access policy. Trial documentation including the protocol are available on request by contacting Formal requests for data sharing are considered in line with ICR-CTSU procedures. Requests are via a standard proforma describing the nature of the proposed research and extent of data requirements. Contact sofea-icrctsu@icr.ac.uk or visit the link below for further information.
• IPD Sharing Time Frame: Data will become available to researchers following the formal review and approval of a data access request in accordance with the ICR-CTSU data and sample access policy.
• IPD Sharing Access Criteria: Completion and approval of a data access request form as stated above
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No