Clinical Update - Breast Cancer
Clinical Update - Issue 18 - December 2004 - ISSN 1328-9454
Anastrozole vs Tamoxifen: Impact on Quality of Life (Atac 2 Year Assessment)
Commentary by Dr Sue-Anne McLachlan
The article:
Fallowfield L, Cella D, Cuzick J et al. Quality of Life of Postmenopausal Women in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Adjuvant Breast Cancer Trial. Journal of Clinical Oncology 2004; 22(21): 4261-4271Reviewer:
Dr McLachlan is a medical oncologist at St Vincent's Hospital Melbourne, a senior lecturer in the Department of Medicine at the University of Melbourne and the Associate Clinical Director of the Familial Cancer Clinic at the Peter MacCallum Cancer Institute. She was also a member of the NBCC working groups for guidelines on advanced breast cancer and management of breast cancer in young women.
In this issue...
- Article summary
- What do these articles add to existing clinical evidence in this area?
- How adequate was the methodology used in addressing the aims of the studies?
- What are the implications of these studies for clinical practice in Australia?
Summary
Abbreviations
Arimidex, Tamoxifen, Alone or in Combination (ATAC); Anastrozole (A); Aromatase Inhibitors (AI); Tamoxifen (T); Combination of Anastrozole and Tamoxifen (C); Confidence Interval (CI); Endocrine Symptoms (ES); Functional Assessment of Cancer Therapy-Breast (FACT-B); Quality of Life (QoL); Trial Outcome Index (TOI).
Study design:
- Participants: 1,021 postmenopausal women with early-stage operable breast cancer all of whom had completed primary treatment; participants were from 116 centres in 10 countries
- Design: Women from the ATAC Adjuvant Breast Cancer Trial who had been randomly assigned to one of three groups based on treatment (5 years of adjuvant treatment with A, T or C) were assessed for QoL using the FACT-B questionnaire and ES subscale assessment of ES at baseline and 3, 6, 12, 18 and 24 months
- Primary endpoint = Fact-B TOI; secondary endpoint = ES total score
- Additional analyses = clinically significant individual ES
Findings
Primary endpoint:
Overall QoL for all groups improved from baseline and there were no significant differences in TOI comparing A vs T
(-0.75; 95% CI, -1.98 to +0.47; p=0.23) or C vs T (-0.10; 95% CI, -1.32 to +1.12; p=0.87) at two years.
Secondary endpoint:
Between baseline and 3 months ES scores worsened for all treatment groups.
At 2 years there were no significant differences in ES for A vs T
(-0.15; 95% CI, -1.02 to 0.73; p=0.74) or C vs T (-0.59; 95% CI, -1.46 to +0.29; p=0.19).
However, there were clinically significant differences in individual ES between A and T.
There were vasomotor symptom advantages for women treated with A. Vaginal discharge was less
common but vaginal dryness, dyspareunia and loss of interest of sex more common with A.
Conclusion
Two years of treatment with A, T or C had a similar overall impact on QoL. Lower rates of recurrence with A vs T in the main ATAC Trial were achieved without compromising QoL.
What do these articles add to existing clinical evidence in this area?
To date there have been surprisingly few systematic reports of patient based outcomes using validated QoL instruments from major breast cancer trials. Traditionally clinician reports of toxicity and adverse events predominate and there is an inference that these parameters will impact on QoL. This is despite evidence that physicians frequently underestimate patients' QoL and the severity of important symptoms. The ATAC and MA-17 studies are innovative in their inclusion of a sub-study to address QoL. This allowed examination of the impact of different adjuvant endocrine treatments from the patients' perspective. These data provide valuable insights that will help women and their clinicians make decisions about therapeutic options in the adjuvant setting.
How adequate was the methodology used in addressing the aims of the studies?
The ATAC study comprehensively investigated QoL using instruments that have been carefully designed and validated. The FACT- B questionnaire includes items relevant to patients with cancer generally, as well as breast cancer specific concerns. The ES subscale was developed for use with the FACT-B and includes items important to women taking endocrine therapies for breast cancer. There was excellent adherence to protocol defined questionnaire completion. Compliance declined slightly from baseline however at all subsequent time points at least 85% of questionnaires were available for analysis. The sub-study sample mirrored the main ATAC study population in demographics and disease and treatment parameters. A primary endpoint was specified a priori and the sample size ensured adequate power to detect a clinically meaningful difference in QoL between the treatment groups (tamoxifen alone, anastrozole alone, tamoxifen and anastrozole).
During the 2 year assessment period most patients showed a clinically significant improvement from baseline in the aggregate of their physical well-being, functional well-being and breast cancer specific concerns, as measured by the FACT-B Trial Outcome Index. Conversely, most patients in each treatment arm experienced a worsening of endocrine-related symptoms at the 3 month assessment relative to baseline. Thereafter these symptoms appeared to stabilize or improve slightly. There were some interesting differences in the reporting of the severity of individual endocrine symptoms among treatment groups. Women taking anastrozole reported fewer cold sweats, but the same number of hot flushes. Although vaginal discharge was reported less often by women taking anastrozole than women taking tamoxifen, significant vaginal dryness was more common on anastrozole, as was dyspareunia and loss of interest in sex.
What are the implications of these studies for clinical practice in Australia?
Data from completed and ongoing clinical trials demonstrate that third generation aromatase inhibitors are emerging as an important component of adjuvant therapy in women with hormone receptor positive breast cancer. While awaiting mature data from these studies some patients and clinicians are electing to use these drugs either as initial therapy in the adjuvant setting or following a course of tamoxifen. QoL data reported in this study provides important information beyond the traditionally described outcomes of cancer drug trials. The clinical benefits of adjuvant anastrozole compared with tamoxifen indicated in the initial findings at two years were achieved without compromising overall QoL. When specific endocrine symptoms were explored some differences were seen. There were vasomotor advantages for women treated with anastrozole. However reports of gynaecological and sexual difficulties were more common on anastrozole. This information will assist women with breast cancer and their clinicians to weigh the risks and benefits when making decisions about endocrine therapies for early stage breast cancer. It may also allow consideration of supportive interventions needed to ameliorate side effects.
Editor: Dr Karen Luxford, Deputy Director NBCC.
Editorial Committee: Mr Max Coleman, Mr John Collins, Dr Sue-Anne McLachlan, Dr Sue Pendlebury, Dr Martin Stockler.
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