In a phase IIb trial reported in JAMA Oncology, Serrano et al found that exemestane at 25 mg three times weekly was noninferior to the standard dosing of 25 mg once daily in terms of serum estradiol reduction among postmenopausal patients with stage 0 to II estrogen receptor (ER)-positive breast cancer who were compliant with study regimens.
In the international, multicenter, double-blind trial, 171 evaluable patients who were candidates for surgery were randomly assigned 1:1:1 between February 2017 and August 2019 to receive exemestane at 25 mg three times weekly (n = 56), once weekly (n = 60), or once daily (n = 55) for 4 to 6 weeks prior to surgery. The primary outcome measure was percentage change in serum estradiol level determined by solid-phase extraction from baseline to final visit prior to surgery, with a noninferiority margin of –6% for the two lower-dose regimens vs the standard regimen.
Key Findings
The least square mean percentage change in serum estradiol was −89% in the once-daily group, −85% in the three-times-weekly group, and −60% in the once-weekly group. The difference in estradiol percentage change between the once-daily group and the three-times-weekly group was −3.6% (P for noninferiority = .37).
Compliance was defined as taking ≥ 80% of prescribed pills. Among 153 compliant patients, the least square mean percentage change in estradiol was −91% in the once-daily group, −92% in the three-times-weekly group, and −69% in the once-weekly group. The difference in estradiol percentage change between the once-daily group and the three-times-weekly group was +2.0% (97.5% lower confidence limit = −5.6%, P for noninferiority = .02). No significant differences in adverse events were observed among patients across the three groups.
The investigators concluded, “In this randomized clinical trial, exemestane [at] 25 mg given three times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in [patients] who do not tolerate the daily dose in the adjuvant setting.”
Andrea DeCensi, MD, of Ospedali Galliera, Genova, Italy, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the National Cancer Institute, Italian Ministry of Health, and others. For full disclosures of the study authors, visit jamanetwork.com.
