In a post hoc analysis from the phase III TAILORx trial reported in JAMA Oncology, Yanez et al identified factors that may be associated with an increased and decreased likelihood of early discontinuation of adjuvant endocrine therapy for breast cancer.
Study Details
"[B]aseline patient-reported health-related quality of life components, such as poor social well-being, poor physical well-being, and comorbid depression, were significant risk factors for early discontinuation of endocrine therapies..."— Yanez et al
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The TAILORx trial, conducted between April 2006 and October 2010, randomly assigned women with hormone receptor–positive, HER2-negative, axillary node–negative breast cancer to receive adjuvant chemotherapy followed by 5 years of endocrine therapy (chemoendocrine therapy) or endocrine therapy alone, with endocrine therapy being started within 1 year of study entry. The trial showed that endocrine therapy was noninferior to chemoendocrine therapy in invasive disease–free survival among patients with midrange 21-gene recurrence scores between 11 and 25.
The current analysis includes the subgroup of 954 women who were enrolled in the patient-reported outcomes substudy in the trial. Patients completed questionnaires on health-related quality of life including physical well-being and social well-being prior to starting endocrine therapy. Early discontinuation of endocrine therapy was defined as discontinuation at up to 4 years unrelated to death or recurrence. Cox proportional hazards regression joint prediction models were used to assess associations between adherence rates and patient-level factors.
Key Findings
Among the 954 women, 106 had early discontinuation of endocrine therapy, yielding an overall 4-year nonadherence rate of 11.4% (95% confidence interval = 9.5%–13.6%).
In a joint model, factors associated with a reduced likelihood of early discontinuation of endocrine therapy were receipt of chemoendocrine therapy vs receipt of endocrine therapy alone (hazard ratio [HR] = 0.57, P = .02) and age older than 40 years vs ≥ 40 years, with hazard ratios of 0.39 (P = .02) for 41 to 50 years, 0.28 (P = .001) for 51 to 60 years, 0.40 (P = .02) for 61 to 70 years, and 0.23 (P = .02) for older than age 70.
In an analysis adjusting for receipt of chemotherapy vs endocrine therapy alone and age, factors associated with an increased likelihood of early discontinuation of endocrine therapy were worse vs better physical well-being (HR = 2.12, P = .002) and worse vs better social well-being (HR = 1.94, P = .006) measured on the Functional Assessment of Cancer Therapy (FACT) scale.
In additional analyses adjusting for receipt of chemotherapy vs endocrine therapy alone and age, history of depression vs no history of depression (HR = 1.82, P = .005) was the sole medical comorbidity associated with early discontinuation of endocrine therapy. The number of non–endocrine therapy medications used at baseline was not associated with endocrine therapy discontinuation; however, use vs no use of antidepressants at baseline was associated with an increased likelihood of early discontinuation (HR = 1.87, P = .003).
The investigators concluded: “In this post hoc analysis of a randomized clinical trial, baseline patient-reported health-related quality-of-life components, such as poor social well-being, poor physical well-being, and comorbid depression, were significant risk factors for early discontinuation of endocrine therapies. These results support systematic screening for patient-reported outcomes and depressive symptoms to identify women at risk for discontinuation of [endocrine therapy].”
Betina Yanez, PhD, of the Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
