Patient-Reported Outcomes and Long-Term Nonadherence to Aromatase Inhibitors

Abstract

Background: Nonadherence to aromatase inhibitors (AIs) is common and increases risk of breast cancer (BC) recurrence. We analyzed factors associated with nonadherence among patients enrolled in S1105, a randomized trial of text messaging.

Methods: At enrollment, patients were required to have been on an adjuvant AI for at least 30 days and were asked about financial, medication, and demographic factors. They completed patient-reported outcomes (PROs) representing pain (Brief Pain Inventory), endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms), and beliefs about medications (Treatment Satisfaction Questionnaire for Medicine; Brief Medication Questionnaire). Our primary endpoint was AI nonadherence at 36 months, defined as urine AI metabolite assay of less than 10 ng/mL or no submitted specimen. We evaluated the association between individual baseline characteristics and nonadherence with logistic regression. A composite risk score reflecting the number of statistically significant baseline characteristics was examined.

Results: We analyzed data from 702 patients; median age was 60.9 years. Overall, 35.9% patients were nonadherent at 36 months. Younger patients (younger than age 65 years) were more nonadherent (38.8% vs 28.6%, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.05 to 2.16; P = .02). Fourteen baseline PRO scales were each statistically significantly associated with nonadherence. In a composite risk model categorized into quartile levels, each increase in risk level was associated with a 46.5% increase in the odds of nonadherence (OR = 1.47, 95% CI =1.26 to 1.70; P < .001). The highest-risk patients were more than 3 times more likely to be nonadherent than the lowest-risk patients (OR = 3.14, 95% CI = 1.97 to 5.02; P < .001).

Conclusions: The presence of multiple baseline PRO-specified risk factors was statistically significantly associated with AI nonadherence. The use of these assessments can help identify patients for targeted interventions to improve adherence.

Figure 1.

Results of logistic regression models with nonadherence at 36 months (±6 months) coded as a binary outcome and the protocol-specified stratification variables AI duration and AI type as covariates. AI type (exemestane vs letrozole vs anastrozole) was coded using indicator variables, with anastrozole as the reference category. Each model was stratified by treatment arm. PRO scores were split at the median value, which is shown in parentheses. Baseline factors included in the PRO-based composite baseline risk score are represented with an asterisk. P values were derived from Wald tests in logistic regression analyses. AI = aromatase inhibitor; BMQ = Brief Medication Questionnaire; BPI = Brief Pain Inventory; CI = confidence interval; ES = endocrine symptoms; FACT-ES = Functional Assessment of Cancer Therapy–Endocrine Symptoms; FACT-G = Functional Assessment of Cancer Therapy–General; M = median; PRO = patients-reported outcomes; TSQM = Treatment Satisfaction Questionnaire for Medicine.

Figure 2.

Distribution of number of baseline risk factors. Patients are categorized into groups based on their number of risk factors at baseline: 0-3, 4-7, 8-10, or 11-14. Risk factors included the 14 nonoverlapping patients-reported outcomes domain scores that were statistically significantly associated with nonadherence, including BPI-SF worst, least, average, and right now pain, and pain interference; FACT functional, emotional, social, and physical well-being and additional ES concerns; BMQ; and TSQM side effects, effectiveness, and global scales. BMQ = Beliefs about Medication Questionnaire; BPI-SF = Brief Pain Inventory Short Form; FACT-ES = Functional Assessment of Cancer Therapy–Endocrine Symptoms; TSQM = Treatment Satisfaction Questionnaire for Medicine.

Figure 3.

Observed rates of nonadherence according to level of risk. Risk factors included the nonoverlapping patient-report outcome domain scores that were statistically significantly associated with nonadherence, including BPI-SF worst, least, average, and right now pain, and pain interference; FACT functional, emotional, social, and physical well-being and additional ES concerns; BMQ; and TSQM side effects, effectiveness, and global scales. P values were derived from Wald tests in logistic regression analyses. BMQ = Beliefs about Medication Questionnaire; BPI-SF = Brief Pain Inventory Short Form; CI = confidence interval; ES = endocrine symptoms; OR = odds ratio; FACT-ES = Functional Assessment of Cancer Therapy–Endocrine Symptoms; TSQM = Treatment Satisfaction Questionnaire for Medicine.