Impact of routine assessment of health-related quality of life coupled with therapeutic information on compliance with endocrine therapy in patients with non-metastatic breast cancer: protocol for a randomized controlled trial

Currently, a large number of hormonal and cytotoxic oral therapies are available for breast cancer (BC) management. The major advantage of these therapies is their convenience due to self-administration [1, 2]. Currently, in cancer treatment, more than 40 oral drug specialties are reimbursed by the French health insurance system [1]. These oral forms present a new challenge in oncology, namely concerning treatment compliance. Compliance is defined as the extent to which the patient follows the prescriber’s recommendations [3]. Oral anticancer therapies raise concerns about poor compliance, particularly the impact of adverse effects due to non-compliance on clinical outcomes. Non-compliance compromises overall efficacy of oral therapies and potentially leads to treatment failure [4].

In BC, the oral form of endocrine therapy (ET) is by far the most widely investigated in terms of compliance [1]. Compliance with oral ET is not optimal in BC. Indeed, only 59% of women who receive ET for BC remain compliant one year after prescription [5] and this percentage ranges between 41% and 72% at the end of 5 years of treatment [6]. Poor compliance with ET is associated with decreased survival [7, 8], increased risk of recurrence [7], and poor prognosis [9]. To improve compliance, several studies [10‐12] have implemented interventions via educational materials (letters, information booklets, and telephone interviews) but none has shown a significant effect. Hadji et al., in their study testing the addition of educational materials to standard therapy versus the standard therapy only in women taking anastrozole, have shown no significant effects on compliance and persistence with adjuvant anastrozole [10]. In a study by Ziller et al., patients receiving additional/supplemental information appeared to have an improved adherence rate, even though differences between groups with regard to the primary endpoint were not statistically significant [11]. In another study, postmenopausal women with hormone receptor–positive (HR⁺) early-stage BC treated with aromatase inhibitors (AIs) were randomly assigned to one of two groups: one receiving only AIs and the other one receiving educational materials plus AIs. This study has shown that education materials do not improve compliance in this patient population and has highlighted the complex nature of compliance and persistence [12].

It is interesting to note that compliance is a multidimensional phenomenon that can result from various factors related to patients (social support, patient beliefs, and psychosocial factors), treatments (side effects), or health-care systems (poor patient–health-care provider relationship) [13].

Evaluation of the quality of care is of major importance, but to date, most quality initiatives have focused on assessing adverse events, clinical processes, and cost variables. Less attention has been given to indicators of clinical improvement measured from the point of view of the patient [14]. To give patients the opportunity to express their perception concerning their own health in clinical trials and routine practice, it is necessary to plan and assess the use of health-related quality of life (HRQoL) in clinical research and practice (Fig. 1).

HRQoL is gathering increasing interest in oncology, as reflected by the number of scales being developed and the increased use of HRQoL measurement as an outcome in randomized controlled trials. Reasons for this growing interest may be related to significant treatment toxicities but also to the fact that HRQoL has been shown to be a prognostic factor for survival [15, 16]. In many cases, symptom palliation of and improvement of HRQoL, rather than increased survival, are the main goals of treatment. Thus, the American Society of Clinical Oncology and the US Food and Drug Administration recommend HRQoL as the second endpoint after overall survival and the primary endpoint of treatment efficacy if treatment has no effect on overall survival. Over the past decade, HRQoL in BC has been widely studied and many determinants have been identified [17, 18].

Routine evaluation of HRQoL was shown to have a positive impact on communication between patients and medical staff [19] and on clinical parameters such as the duration of treatment without relapse and survival [20, 21]. Recently, it has been suggested that there may be a link between HRQoL and compliance with oral ET. Indeed, Pinheiro et al. reported that women with poorer HRQoL were more likely at risk of non-adherence [22] in a study addressing the association between HRQoL and under-use of ET in women with hormone-sensitive BC. This result suggests that focusing on a modifiable factor such as HRQoL could be a way to improve compliance with oral ET. In addition, to date, the modulatory effect of HRQoL on compliance with oral treatments in BC has not been studied.

With the advent of digital technologies, it is now possible to perform HRQoL measurements using a tablet with instantaneous score generation [23]. This mode of measurement provides real-time results to clinicians (through graphics) and generates alerts (color codes) if HRQoL scores are deteriorated, allowing adjustment of patient support in a personalized way. From the patient’s point of view, the inclusion of numerical assessment in the process of data collection has shown benefits in disease management and symptom control [24], improving survival [20] and patient-clinician communication [19]. Moreover, it potentially facilitates clinical decision making through the systematic and continuous collection of symptom data [25].

Since compliance is a multidimensional phenomenon, any attempt to improve it should encompass several potential contributors. Thus, we hypothesize that electronic measurement of HRQoL (before each consultation with scores communicated immediately to clinicians who can discuss it with patients), coupled with therapeutic information, will improve 12-month compliance rate with ET in patients with non-metastatic BC. At a later step, we will assess the role of social support and psychological distress as potential modulators of compliance with ET, the capacity of HRQoL to predict compliance with ET, patient satisfaction with care, and physician perception regarding the clinical utility of routine HRQoL evaluation.

To achieve study aims, we will carry out a randomized, interventional, prospective study. Patients will be recruited at the Dijon cancer center (Georges François Leclerc-Unicancer Centre) in France. This center is specialized in cancer management; therefore, clinicians are experienced in patient HRQoL evaluation and are accustomed to take this criterion into consideration in routine patient management.

Women who are at least 18 years old and have non-metastatic HR⁺ BC will be included in this study. These women will have to be at the end of primary treatment, have an indication for ET treatment during 5 to 10 years, be affiliated with a French social security scheme or the beneficiary of such a scheme, and have agreed to participate by providing written consent. Patients who participate in another clinical trial where HRQoL is assessed will not be included, nor will women for whom HRQoL evaluation is not possible (cognitive disorders, psychiatric disorders, and people who do not speak French).

This study will evaluate the usefulness of systematic assessment of HRQoL coupled with therapeutic information to enhance compliance with ET in patients with non-metastatic BC. To take into account that compliance decreases over time, a reminder to encourage patients to take ET was included in the intervention and will be sent every month. A steering committee has also been set and will be responsible for all decisions concerning the study.

In the future, if results are positive, this intervention will be implemented in clinical practice; therefore, we have chosen to be as close as possible to routine clinical practice. Routinely, women with HR⁺ BC treated with ET will have a consultation two or three times a year. HRQoL will be assessed before each consultation and will be monitored three times during study duration.

This routine HRQoL assessment would enable clinicians to identify and better understand the areas in which patients who receive ET most need support, therefore guiding patient individual management. Systematic assessment of HRQoL could provide an additional endpoint for measuring patient status and treatment-related symptoms, including ET.

If study results are positive, electronic assessment of HRQoL coupled with therapeutic information could be offered in daily clinical practice as an integral part of the care process for patients who receive ET. Moreover, this intervention could be generalized to other centers in France given that every cancer center has a service dedicated to therapeutic information.

Protocol version 1.1. Date: Aug. 20, 2019. Recruitment began in January 2020 and will be completed by around December 2022.