Abstract OT1-11-02: A pragmatic, randomised, multicentre trial evaluating the dose timing (morning vs evening) of endocrine therapy and its effects on tolerability and compliance (REaCT-CHRONO Study)

Abstract

Background. Endocrine therapy (ET) is the mainstay treatment for hormonal receptor positive (HR+) breast cancer. ET non-compliance and non-persistence vary from 30 to 70% and are associated with reduced disease-free and overall survival. ET side effects are an important cause of non-adherence. In clinical practice, there are anecdotal reports that time of the day at which ET is taken may affect ET side effects and compliance. However, we are not aware of any high-quality studies supporting this practice. In other fields of medicine, there is evidence to suggest that the time of the day at which medication is taken can alter its effect and/or the adherence. This is known as chronotherapy. Methods. In this pragmatic, open-label, multicenter trial, eligible and consented patients with an early stage or locally advanced HR+ breast cancer will be randomized (1:1) to receive either: an ET morning dose (Arm A: within 1 hour of the patient wake up time) or an ET evening dose (Arm B: within 1 hour of patient bed time). The primary endpoint is endocrine toxicity and tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline to 12 weeks following the beginning of ET. Secondary endpoints include: endocrine toxicity/tolerability and quality of life measured respectively by the change in total score and individual items of FACT-ES and FACT-B (a validated Functional Assessment of Cancer Therapy for patients with a Breast cancer) from baseline to 4, 8, 12 and 52 weeks following the beginning of ET, rates of non-persistence or non-compliance and cost-effectiveness. A timing preference questionnaire will be filled out at the beginning and the end of the study by patients to evaluate their preferred time. As per the Rethinking Clinical Trials (REaCT) program, the integrated consent model will be used and patients will complete questionnaires in the online patient portal. For randomization, a permuted block design developed by the Ottawa Methods Centre will be used and patients will be stratified by center, type of endocrine therapy (tamoxifen yes/no) and if prior chemotherapy was received. Using a two-sided, alpha=0.05 Fisher’s exact test, and assuming a 10% of loss to follow up, the planned sample size is 235 patients. Accrual. This study opened for enrollment at The Ottawa Hospital Cancer Centre on June 30, 2021 and will open soon at the Thunder Bay Regional Health Sciences Centre. The maximum accrual period is 2 years. Conclusion. This will be world’s first prospective randomized clinical trial to evaluate ET dose timing (morning versus evening) and its effects on tolerability and adherence. Changing the time of the day at which a medication is taken is a new, simple and easy intervention that does not generate additional costs and can improve the quality of life of breast cancer patients. Funding provided by: NOAMA (Northern Ontario Academic Medicine Association) Innovation Grant (2021) Clinical Trial Registration: NCT04864405 Citation Format: Marie-France Savard, Mohammed Ibrahim, Gregory Pond, Deanna Saunders, Lisa Vandermeer, Ana-Alicia Beltran-Bless, Lesley Fallowfield, Mark Clemons. A pragmatic, randomised, multicentre trial evaluating the dose timing (morning vs evening) of endocrine therapy and its effects on tolerability and compliance (REaCT-CHRONO Study) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-11-02.

Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial

“… 19 A pragmatic randomized trial comparing morning versus evening dosing of endocrine therapy for early breast cancer (REaCT-CHRONO Study) was presented at San Antonio breast cancer symposium in 2023 and found no difference in the effects of ET timings on ET intake compliance or quality of life. 26 …”

The REthinking Clinical Trials Program Retreat 2023: Creating Partnerships to Optimize Quality Cancer Care

“…Between June 2021 and March 2022, 245 eligible patients were randomized (16). The results showed no significant difference in endocrine therapy toxicity and tolerability between the morning and evening timings of endocrine therapy (Table 1, Figure 1) (16).…”

“…No prospective evidence exists for whether the time of day of administration affects endocrine side effects. The REaCT-CHRONO study randomized patients receiving adjuvant endocrine therapy to either morning or evening doses of endocrine therapy [ 15 ]. The primary endpoint was endocrine therapy toxicity and tolerability measured by the change in the total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from the baseline to 12 weeks following the beginning of ET.…”

“…The results showed no significant difference in endocrine therapy toxicity and tolerability between the morning and evening timings of endocrine therapy ( Table 1 , Figure 1 ) (16). The secondary endpoint results, including the 12-month adherence rate and patient quality of life, were presented in a later symposium in 2023 [ 16 ].…”