Early Endocrine Therapy Discontinuation Linked to Certain Baseline Well-Being Factors

Patients who discontinued endocrine therapy early were more likely to have experienced significant mental, physical, and social adverse effects of treatment.

Early discontinuation of endocrine therapy (ET) was associated with poorer baseline health-related quality-of-life factors such as poor social and physical well-being as well as comorbid depression in women with hormone receptor–positive, HER2-negative breast cancer, according to a study published in JAMA Oncology.

In this post hoc analysis of the TAILORx trial (NCT00310180), patient-reported were used to identify those at highest risk of ET discontinuation. In total, 954 patients with breast cancer treated between April 2006 to October 2010 were identified for the substudy.

“Elucidating the factors that are associated with ET discontinuation is an important first step in improving adherence to ET,” said investigators about the study. 

Patients who discontinued ET early were defined as those stopping treatment for any reason other than death or recurrence. Investigators used Kaplan-Meier estimates for determining rates of discontinuation. To correlate rates of ET adherence and patient-level factors, Cox proportional hazards regression joint prediction models were used. Patient-level factors specified in the study were age, race, treatment type, and Oncotype Dx recurrence score. For this analysis, investigators included a control group of patients with the lowest health-related quality of life. 

Out of all women studied, there were 106 cases of early ET discontinuation, resulting in an overall 4-year nonadherence rate of 11.4% (95% CI, 9.5%-13.6%). Patients who were less likely to have early ET discontinuation included those receiving chemoendocrine therapy versus ET alone (HR, 0.57; 95% CI, 0.35-0.92; P = .02) and those over the age of 40 years, with statistical significance varying across age groups of 41 to 50 years (HR, 0.39; 95% CI, 0.18-0.85; P = .02), 51 to 60 years (HR, 0.28; 95% CI, 0.13-0.60; P = .001), 61 to 70 years (HR, 0.40; 95% CI, 0.18- 0.86; P = .02), and 70 years or more (HR, 0.23; 95% CI, 0.07-0.77; P = .02).

Patients who had worse physical (HR, 2.12; 95% CI, 1.30-3.45; P = .002) and social (HR, 1.94; 95% CI, 1.20-3.13; P = .006) wellbeing were significantly more likely to experience early discontinuation of ET vs patients reporting positive functioning.

The only medical comorbidity associated with early discontinuation in this study was a history of depression versus no history (HR, 1.82; 95% CI, 1.19-2.77; P = .005) after adjusting for factors such as treatment received and age. Additionally, patients who received antidepressants were more likely to experience early discontinuation of ET vs those who did not (HR, 1.87; 95% CI, 1.23-2.84; P = .003).

“More specifically, our findings suggest that oncology clinicians should consider referral for psychosocial care or physical rehabilitation for patients at risk for early discontinuation of ET,” investigators of the study said of the findings.

In the initial findings from TAILORx, investigators found that patients over 50 years of age with 21-gene recurrence scores between 11 and 25 had noninferior outcomes with ET alone vs ET plus chemotherapy. In turn, these patients safely avoided the adverse effects and comorbidities associated with chemotherapy.

Reference

Yanez B, Gray RJ, Sparano JA, et al. Association of Modifiable Risk Factors With Early Discontinuation of Adjuvant Endocrine Therapy: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Oncol. Published online June 17, 2021. doi:10.1001/jamaoncol.2021.1693