Quality-of-Life Study in NCIC MAP.3 Trial Shows Limited Negative Impact of Daily Exemestane in Breast Cancer Prevention
The National Cancer Institute of Canada (NCIC) Clinical Trials Group MAP.3 (Mammary Prevention 3) trial showed that daily exemestane treatment reduced invasive breast cancer risk by 65% among postmenopausal women. In a quality-of-life study in the MAP.3 population reported in the Journal of Clinical Oncology, Maunsell et al found that exemestane was associated with small negative effects on vasomotor symptoms, sexual symptoms, and bodily pain, reflecting clinically important worsening in a small excess of subjects compared with placebo.
Study Details
In MAP.3, 4,560 postmenopausal women were randomly assigned to receive oral exemestane at 25 mg or placebo once daily for up to 5 years. Menopause-specific and health-related quality of life were assessed using the four Menopause-Specific Quality of Life Questionnaire (MENQOL) domains (vasomotor, sexual, physical, psychosocial) and the eight Medical Outcomes Study Short Form Health Survey (SF-36) scales (bodily pain, physical health, general health, role function-physical, mental health, vitality, social function, role function-emotional) and component summaries (physical component, mental component) at baseline, 6 months, and yearly thereafter.
Change scores for MENQOL and SF-36 scales calculated at each time point relative to baseline were compared using the Wilcoxon rank-sum test. Clinically important worsening of quality of life was defined as a MENQOL change score increase of > 0.5 (of 8) points and an SF-36 change score reduction of > 5 (of 100) points from baseline.
The two groups had similar MENQOL domain and SF-36 scale and component summary scores at baseline. Compliance with quality-of-life assessments was 88% to 94% in the exemestane group and 91% to 94% in the placebo group between 6 months and 5 years.
Almost No Clinically Important Differences Between Groups
Women receiving exemestane consistently had significantly higher vasomotor change scores (all P < .01), with the symptom scores being greatest at 6 months and decreasing thereafter; however, the between-group differences in change scores were not clinically significant. Change scores in the MENQOL sexual, physical, and psychosocial domains tracked similarly in both groups, with almost all between-group differences in change scores being ≤ 0.1 point.
Women in the exemestane group also had consistently higher SF-36 bodily pain scores starting at 6 months and continuing throughout the study, with the change score approaching the threshold for a clinically important change at 2 and 3 years and exceeding it by 4 years and beyond. However, the greatest net between-group difference in pain change scores, observed at 2 years, was 1.85 (lower than the 5-point criterion for clinically important). Except for social functioning at 4 years, the mean change scores for all other SF-36 scales were similar in both groups, with net between-group differences well below the 5-point threshold.
Proportions With Clinically Important Worsening
Worsening that met the criteria for clinical importance was significantly more common (all P < .05) in the MENQOL vasomotor (39% vs 29%) and sexual (20% vs 17%) domains at 6 months, through 1 year (49% vs 39%; 29% vs 26%), and overall (55% vs 47%; 39% vs 35%). On the SF-36, significantly more exemestane patients had clinically important worsening in bodily pain at 6 months (41% vs 37%), through 1 year (56% vs 51%), and overall (66% vs 62%) and in vitality at 6 months (45% vs 43%).
Overall, 32% of women receiving exemestane and 28% receiving placebo discontinued study treatment, mainly reflecting the greater proportion stopping exemestane within 6 months (10.4% vs 6.5%).
The investigators stated, “Exemestane had small negative effects on women’s self-reported vasomotor symptoms, sexual symptoms, and pain, which occurred mainly in the first 6 months to 2 years after random assignment. However, these changes represented only a small excess number of women being given exemestane with clinically important worsening of [quality of life] at one time or another; specifically, 8% more in the vasomotor domain and 4% more each in the sexual domain and for pain.”
They concluded, “Exemestane given for prevention has limited negative impact on menopause-specific and health-related [quality of life] in healthy postmenopausal women at risk for breast cancer.”
Elizabeth Maunsell, PhD, of Hôpital du Saint-Sacrement, Quebec, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by the Canadian Cancer Society Research Institute, Canadian Institutes of Health, Avon Foundation, and Pfizer Pharmaceutical. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
