Year: 2023
Type: article
Abstract: In this issue of JAMA Oncology, Serrano et al present results of a phase 2b trial of postmenopausal women with early-stage breast cancer assessing change in serum estradiol levels and breast tumor Ki-67 after 4 to 6 weeks of 3-times-weekly or once-weekly exemestane reduced-frequency regimens vs the standard 25 mg daily. 1 The primary end point was the noninferiority of change in serum estradiol between the reduced-frequency and standard-frequency arms when estradiol was measured by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry.The 3-times-weekly and once-weekly dosing regimens were selected based on prior observations of exemestane's long half-life (27 hours) and at least partial suppression of aromatase activity 9 days after a single 25-mg dose.For women who were compliant with prescribed dosing, the mean relative change in estradiol was -91% for the 3-times-weekly regimen vs -92% for daily exemestane. 1 Noninferiority was defined as having 97.5% confidence that the reduced-frequency regimens did not differ from the daily regimen in estradiol suppression by more than a relative 6%.Consequently, at least for women who were 80% compliant with their dosing, noninferiority was demonstrated for the 3-times-weekly regimen but not the once-weekly regimen (-69% mean change).Similar numerical changes were noted for the intent-to-treat (ITT) analyses.However, the 97.5% CI boundary could not be excluded, and thus the 3-times-weekly regimen could not be considered noninferior by the ITT analysis.No difference was observed among regimens in incidence or severity of adverse events, but treatment duration was likely too short to observe differences, particularly in musculoskeletal symptoms, one of the most frequent causes of aromatase inhibitor (AI) discontinuation. 2 The authors suggest that the 3-times-weekly regimen should be studied further in longerduration primary prevention and adjuvant therapy trials. 1 Should we take their advice, given the inability to demonstrate noninferiority in the ITT analysis of the primary efficacy biomarker or difference in adverse events between the standard and 3-times-weekly arms?
Source: JAMA Oncology
Authors: Carol J. Fabian, Dinesh Pal Mudaranthakam
Institution: University of Kansas Medical Center
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4360601105