The Effect of Exemestane on Menopause-Specific Health-Related Quality of Life and a Comparison With Clinician-Reported Toxicities: an Analysis of the NCIC CTG MAP.2 Chemoprevention Trial
Causarano, Natalie Cristina
Cancer Prevention , Patient-Reported Outcomes , Adverse Events , Health-Related Quality of Life , Clinical Trials
Background: Exemestane is a drug of great interest for breast cancer prevention, because it inhibits estrogen production. Estrogen may operate by increasing breast density, a well-established biomarker for increased breast cancer risk. The NCIC CTG MAP.2 trial examined the efficacy of exemestane in decreasing breast density. Menopausal health-related quality of life (HRQL) and adverse events were also carefully monitored during the study. Purpose: To elucidate the impact of exemestane on menopausal HRQL and to examine the relationship between clinician and participant methods of reporting side effects. Methods: 98 postmenopausal women with increased breast density were randomized to exemestane or placebo daily for one year. HRQL was measured with the MENQOL questionnaire, which has four domains. Mean changes in MENQOL domain scores from baseline were compared between treatment groups using the Wilcoxon rank-sum test. The difference between groups in the proportion of women with a clinically meaningful decline was compared by domain with the Chi-square test; change scores were considered worsened if increased by ≥ 0.5 points. The association between time-to-decline in menopausal HRQL and treatment was evaluated using Cox PH regression. The kappa statistic quantified the level of agreement between participant-reported and clinician-reported symptoms. Kaplan-Meier estimates of time-to-decline as communicated by clinicians and participants were compared, using three thresholds to define meaningful change. Results: No significant differences in mean change scores were detected, however, a significantly greater proportion of women on exemestane experienced a clinically meaningful decline in physical menopausal HRQL at three months (absolute difference=19%, p= 0.03), while the absolute difference approached significance for vasomotor menopausal HRQL at six months (21%, p= 0.05), and at nine months (21%, p=0.06). The rate of decline in physical menopausal HRQL was 2.08 times greater (95% CI 1.10-3.94) in the exemestane group compared to the placebo group. Agreement between raters was low for all symptoms except hot flashes; in general participants detected symptoms more rapidly than clinicians, regardless of the defined cut-off for meaningful change on the MENQOL. Conclusions: A subset of women on exemestane experienced significant declines in physical and vasomotor symptoms. Generally, participants reported symptoms more frequently and faster than clinicians.