Abstract P1-12-12: Bubble packaging of adjuvant endocrine therapy:updated analysis of compliance and survival
Authors: Bhandari S , Ngo PT , Mandadi M , Wu X , Brown C , Rai S , Riley EC 
Published: May 2019

Abstract
Introduction: Adherence to endocrine therapy is a long recognized problem despite efficacy of these drugs with reported compliance rates of 89% in first year and 50% in fourth year. Most of our knowledge of noncompliance is observational and retrospective. This final analysis of the Bubble Study reports the compliance rate of adjuvant endocrine therapy among women with early stage breast cancer using “bubble” packaging. We previously reported adherence rates of 97% with bubble packaging. This updated analysis includes disease free survival (DFS) and overall survival (OS) at 5 years.
Methods: The Bubble study is a non-blinded, prospective observational cohort study, which enrolled 86 patients between August 2012 and April 2014. Demographic and clinical data were collected prospectively including age, race, insurance, duration of therapy, stage, treatment, comorbidities, recurrence and survival. Duration of therapy was divided into 3 cohorts: &lt;12 months, 12-36 months, and 37-60 months. All patients received routine prescriptions in a “bubble” pack or daily blister pack. Patients returned all used bubble packs at follow up appointments for review and kept a diary of missed doses for analysis. DFS and OS data were obtained at 78 months. Compliance was defined as &gt;90% adherence. We calculated institutional DFS and OS for breast cancer patients treated within a similar time frame from the tumor registry.
Results: 53 patients were included in the analysis. The remaining patients withdrew from the study prior to data collection or were deemed ineligible. The overall compliance rate was 97%; however, only 72% of enrolled patients were continued in the analysis. None of the variables examined (race, age, insurance status and stage) had an impact on compliance. Only duration of endocrine therapy had a marginal effect on compliance (p value = 0.06). The latest cohort (duration of therapy 37-60 months) was least likely to be compliant at 89.53%. Our 5-year DFS is 92% and 5-year OS is 96%. There is no statistically significant difference in DFS and OS between patients with compliance&gt;90% and &lt;90%. For ER+ breast cancer patients treated during similar timeframe at our institution outside the trial, 5-year DFS is 94% and 5-year OS is 90%.
Conclusion: There was no difference in OS or DFS based on compliance to oral anti-estrogens. Given the high overall compliance rate in this small patient population, the lack of OS and DFS difference is not surprising. However, the compliance rate of bubble packaging (&gt;90%) is higher than expected based on current literature. Although this may suggest improved compliance with bubble packaging, more studies are necessary to confirm this given small sample size and high trial dropout rate. Trial withdrawal likely altered analysis of adherence rates as it selects for a largely compliant group of patients.This bias may also explain the lack of difference in compliance rate among race, insurance status and/ or age, which contradicts our current knowledge of high-risk groups.There was a trend towards lower DFS in the bubble cohort, but overall better survival when comparing to institutional rate. Studies are ongoing to confirm bubble packaging adherence rates and compare this to established strategies to improve adherence.
Citation Format: Bhandari S, Ngo PT, Mandadi M, Wu X, Brown C, Rai S, Riley EC. Bubble packaging of adjuvant endocrine therapy:updated analysis of compliance and survival [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-12.