Fulvestrant Monotherapy After CDK4/6 Inhibitors in Metastatic Breast Cancer Patients: A Real-Life Experience.

Background: The treatment of hormone receptor positive (HR+), HER-2 negative metastatic breast cancer (MBC) has radically changed over the last few years. CDK4/6 inhibitors combined with endocrine therapy have become the standard of care as a front-line therapeutic approach, conferring a significant improvement in progression-free survival and overall survival compared to traditional endocrine therapy (ET) alone. However, the wide administration of these drugs in clinical practice paved the way for the emergence of new intrinsic and acquired mechanisms of resistance that seem to compromise second-line treatment effectiveness. In this context, fulvestrant monotherapy appears disqualified. Materials and Methods: we evaluated a population of 30 women currently treated in our oncology unit with HR+/HER2- metastatic breast cancer, receiving fulvestrant 500 mg every 28 days after progression to first-line therapy with CDK 4/6 inhibitors combined with aromatase inhibitors. Results: Of 30 patients observed, 23 progressed to fulvestrant with a median PFS of 3.7 months (range 1-9.7 months). Conclusions: our real-life experience suggests that second-line fulvestrant monotherapy confers very poor disease control and is quite an inadequate therapeutic option. CDK4/6i administration beyond progression could possibly be considered as more valid option, in the absence of targetable mutations or newer, more effective drugs.