Efficacy and Safety of Oral 5-FU Derivatives After Progression of HR⁺/HER2⁻ Metastatic Breast Cancer on CDK4/6 Inhibitor

Background/Aim: Optimal treatment strategies following disease progression on cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET) for patients with hormone receptor-positive (HR⁺) and human epidermal growth factor receptor 2-negative (HER2⁻) metastatic breast cancer (MBC) remain undefined. Oral 5-fluorouracil (5-FU) derivatives, such as tegafur/gimeracil/oteracil (S-1) and capecitabine, are widely used and offer convenience of administration. This study aimed to evaluate the efficacy and safety of oral 5-FU derivatives in such a treatment setting in patients with HR⁺/HER2⁻ MBC.

Patients and Methods: We retrospectively analyzed 40 patients with HR⁺/HER2⁻ MBC who received oral 5-FU derivatives following progression on CDK4/6i plus ET. Clinical outcomes including time to treatment failure and adverse events were assessed.

Results: Of the 40 patients, 97.5% received abemaciclib, and 95.0% were treated with S-1. The median time to treatment failure was 12.3 (range=1.2-29.2) months. Grade 3 adverse events noted were reduced neutrophil count, anemia, alanine aminotransferase increase, and generalized edema, which led to dose reduction but did not result in treatment discontinuation.

Conclusion: These findings highlight the potential of oral 5-FU derivatives as effective and safe treatment options to use after progression on CDK4/6i plus ET for patients with HR⁺/HER2⁻ MBC.