SWIVEL: A randomized phase II trial of switching medications versus guideline-directed interventions for adjuvant aromatase inhibitor side effects in breast cancer patients.

Abstract

TPS12171 Background: Approximately half of breast cancer patients do not complete the standard 5-year course of adjuvant hormone therapy due to side effects, a finding associated with increased recurrence rates and breast cancer-specific mortality. In clinical practice, side effects are commonly addressed by switching to an alternative hormone therapy; however, this strategy has not been prospectively evaluated. In prior retrospective work, adherence was significantly lower among patients who switched therapies compared with those who remained on the same therapy and received treatment for side effects (62% vs 91%, p=0.013); however, interpretation is limited by the retrospective design. Therefore, a prospective randomized clinical trial was initiated to address this evidence gap by directly comparing medication switching with guideline-directed symptom management. Methods: SWIVEL is an ongoing phase II randomized trial comparing medication switching with guideline-directed interventions for the management of aromatase inhibitor side effects. Eligible patients are postmenopausal women or men with stage I–III ER-positive/HER2-negative breast cancer who are planning to initiate aromatase inhibitor monotherapy in the adjuvant setting. Upon enrollment, participants will be screened every 4 weeks with a validated single-item questionnaire (FACIT/GP5). Those who respond that they are ‘quite a bit’ or ‘very much’ bothered by side effects of treatment will be randomized to either (1) switch to a different hormone therapy, which may include an alternative aromatase inhibitor or tamoxifen, or (2) initiate an evidence-based intervention for side effects in accordance with NCCN guidelines and patient-provider preference. Participants may crossover between strategies at any time. The primary outcome is change in patient-reported symptom burden at 3 months following randomization or at crossover, whichever occurs first, measured by the FACT-ES survey. Secondary outcomes include patient-reported symptom burden at 6 months assessed in an intention-to-treat analysis using FACT-ES and PROMIS measures, and medication adherence assessed at 3, 6, 12, and 24 months using a multi-modal approach incorporating validated patient-reported measures (VOILS), pharmacy records, and urine testing for drug metabolites. Additional outcomes include patient-reported quality of life (FACT-G) and sexual function (FSFI), factors associated with adherence including access to care among rural communities, and evaluation of a novel screening tool to identify patients at higher risk for non-adherence. The study is open at Dartmouth Health and has enrolled 7 of 200 planned participants (NCT# 07071038). Clinical trial information: RCT07071038 .