Inter-Group Exemestane Study (IES)

Randomised double-blind trial in postmenopausal women with primary breast cancer who have received adjuvant Tamoxifen for 2-3 years, comparing treatment until 5 years with adjuvant Exemestane versus further Tamoxifen

Trial Governance

 The trial is run by the ICCG in collaboration with the Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) under the auspices of the Breast International Group. The Coordinating Data Centre (CDC), based at Imperial College's Charing Cross Campus, oversees the overall conduct of the trial. 20 globally located co-operative groups (defined as local data centres) are responsible for the trial at a local level. The trial is governed by an international steering committee made up of representatives from the 20 co-operative groups, the chief investigator, the trial statisticians, the project manager and sponsor representatives. The trial is overseen by an Independent Data Monitoring Committee.

Design

 An inter co-operative group, multi-centre, international, randomised, double-blind study

Schema

 

Recruitment

 4724 post-menopausal women from 37 countries were randomized between 1998 and 2003.

Results

 The results of the 2nd interim analysis of efficacy were published in the New England Journal of Medicine in March 2004 on the recommendation of the Independent Data Monitoring Committee. This early release of results was prompted by a highly significant early disease free survival benefit, which exceeded the predefined statistical stopping boundary. An updated analysis published in the Lancet in February 2007 reported, in addition to a continued disease free survival benefit, a modest but real benefit in terms of overall survival.

Trial Status

 In active follow-up. Median follow-up is now approximately 5 years.

Sub-protocols:  

Quality of Life (QoL) Sub-protocol - coordinated by Sussex Psychosocial   Oncology Group led by Prof Lesley Fallowfield. 582 patients were recruited in 8 countries between March 2000 and February 2002. The aim of the study is to compare QoL between the two treatment arms. Results of the 24 month analysis published in the Journal of Clinical Oncology in 2006 indicate that the clinical benefits of exemestane over tamoxifen are achieved without significant detrimental effect on QoL. The final analysis of this data is expected in 2007.

Endometrial Sub-protocol - coordinated by the CDC at Imperial College.  219 patients in 25 centers worldwide were recruited between September 1998 and August 2001. The aim of the study is to assess endometrial ultrasound changes in both treatment groups. The first analysis conducted in 2004 showed that exemestane had no adverse impact on uterine health and some tamoxifen induced negative changes were rapidly reversed. The final analysis of this data is expected in 2007.

Bone Sub-protocol - coordinated by the Bone Central Evaluation Facility of The Department of Biosurgery & Surgical Technology at Charing Cross Hospital. 206 patients from 17 centers worldwide were randomised between March 2000 and February 2003. The aim of this study is to compare bone mineral density (BMD) in lumbar spine and proximal femur and bone metabolism markers between both treatment arms. Results of the 24 month analysis published in Lancet Oncology in February 2007 showed that no patient with normal BMD at randomisation became osteoporotic during the 24 months of the trial. Incidence of fractures was similar in both groups. The most significant loss in BMD was recorded at 6 months after the switch from tamoxifen to exemestane. The final analysis of this data is expected in 2008.