Early participant-reported symptoms as predictors of adherence to anastrozole in the International Breast Cancer Intervention Studies II

I Sestak, S G Smith, A Howell, J F Forbes, J Cuzick, I Sestak, S G Smith, A Howell, J F Forbes, J Cuzick

Abstract

Background: Anastrozole reduces breast cancer risk in women at high risk, but implementing preventive therapy in clinical practice is difficult. Here, we evaluate adherence to anastrozole in the International Breast Cancer Intervention Study (IBIS)-II prevention and ductal carcinoma in situ (DCIS) trials, and its association with early symptoms.

Patients and methods: In the prevention trial, 3864 postmenopausal women were randomized to placebo versus anastrozole. A total of 2980 postmenopausal women with DCIS were randomized to tamoxifen versus anastrozole. Adherence to trial medication was calculated using the Kaplan-Meier method and all P-values were two-sided.

Results: In the prevention trial, adherence was 65.8% [anastrozole (65.7%) versus placebo (65.9%); HR = 0.97 (0.87-1.09), P = 0.6]. Adherence was lower for those reporting arthralgia in the placebo group (P = 0.02) or gynecological symptoms in the anastrozole group (P = 0.003), compared with those not reporting these symptoms at 6 months. In the DCIS study, adherence was 66.7% [anastrozole (67.5%) versus tamoxifen (65.8%); HR = 1.06 (0.94-1.20), P = 0.4]. Hot flashes were associated with greater adherence in the anastrozole arm (P = 0.02). In both studies, symptoms were mostly mild or moderately severe, and adherence decreased with increasing severity for most symptoms. Drop-outs were highest in the first 1.5 years of therapy in both trials.

Conclusions: In the IBIS-II prevention and DCIS trials, over two-thirds of women were adherent to therapy, with no differences by treatment groups. Participants who reported specific symptoms in the IBIS-II prevention trial had a small but significant effect on adherence, which strengthened as severity increased. Strategies to promote adherence should target the first year of preventive therapy.

© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Figures

Figure 1.
Figure 1.
Kaplan–Meier plots for non-adherence and annual non-adherence rates (%) according to treatment arm for the IBIS-II prevention (A, B) and DCIS (C, D) studies. Kaplan–Meier curves were calculated and tested for equality using log-rank test. All statistical tests were two-sided. IBIS, International Breast cancer Intervention Study; HR, hazard ratio; CI, confidence interval.
Figure 2.
Figure 2.
Forest plots for non-adherence (hazard ratios) among women reporting symptoms at 6 months by treatment arm for the IBIS-II prevention (A) and DCIS (B) studies. The squares represent the point estimates. Sizes of the squares represent the number of events. The horizontal error bars show the 95% confidence intervals (CI) of each hazard ratio. IBIS, International Breast cancer Intervention Study; CI, confidence interval.

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