Premature Aromatase Inhibitor Discontinuation Is Common

N. Lynn Henry, MD, PhD

Roughly one-third of women with early-stage breast cancer develop intolerable adverse effects during aromatase inhibitor (AI) therapy, new data revealed. However, the results also showed that more than a third of patients who experienced severe symptoms while taking the first AI were able to tolerate a different AI.

N. Lynn Henry, MD, PhD, with the University of Michigan Comprehensive Cancer Center, Ann Arbor, and associates elsewhere analyzed responses to symptom questionnaires completed by postmenopausal women with stage 0 to III hormone receptor (HR)-positive breast cancer who were randomized to two years’ treatment with exemestane or letrozole as part of the phase IV Exemestane and Letrozole Pharmacogenetics (ELPh) trial.

While AI treatment prolongs disease-free survival compared with tamoxifen and is recommended in postmenopausal women with early-stage HR-positive breast cancer, aromatase inhibition is commonly associated with toxicities that decrease adherence and persistence with therapy, the researchers pointed out. Predictors of early treatment cessation have not been identified.

Study participants completed symptom questionnaires at baseline and after 1, 3, 6, 12, and 24 months. The primary endpoint of the study was primary persistence with the second AI medication after discontinuation of the initial AI medication because of toxicity.

Of 500 eligible patients, 163 (32.4%) stopped therapy because of adverse effects. Musculoskeletal symptoms were the main reason cited by patients for stopping treatment and resulted in treatment discontinuation in 24.3% of patients. The median time to treatment discontinuation as a result of symptom onset was 6.1 months. Patients younger than age 55 years (hazard ratio [HR] = 1.4; 95% CI, 1.02-1.9; P = .04) and patients who received taxane-based chemotherapy (HR = 1.9; 95% CI, 1.00-3.6; P = .048) had a higher likelihood of discontinuing treatment.

Women who chose to stop AI treatment early because of intolerable symptoms were allowed to switch to the other study drug after a two- to eight-week washout phase. Of the 83 patients who crossed over to the second AI, 32 (38.6%) remained on the alternate AI for a median of 13.7 months.

The researchers said that their data are in line with prior studies reporting poor adherence and persistence with adjuvant endocrine therapy. However, unlike earlier studies, this investigation showed that exemestane was associated with a shorter time to cessation of initial AI therapy than letrozole. In the present study, the same trend in higher premature treatment discontinuation rates with exemestane treatment was also observed in the crossover cohort.

The authors also commented that the ability of more than one-third of women to tolerate a second AI after not being able to tolerate the initial AI is an important finding. They acknowledged that it may be that patients who decided to switch to the alternate AI did so because they were more motivated, which led to a higher percentage of patients being able to tolerate the second AI.

“Regardless, this is still a reasonable strategy to use in the clinic, because our results demonstrate that a subset of patients will be able to continue AI therapy despite intolerance of the initial AI,” the authors wrote.

Henry NL, Azzouz F, Desta Z, et al. Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer [published online ahead of print February 13, 2012]. J Clin Oncol. 2012;30(9):936-942.