248P Systemic treatment strategies following progression on CDK4/6 inhibitors in advanced breast cancer: A single-center real-world experience

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) are the standard of care treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- aBC). However, optimal treatment after progression on CDK4/6i has not been established and real-world data may help to fill this knowledge gap. Two hundred twenty-one patients with HR+/HER2- aBC treated with CDK4/6i plus ET at Medical Oncology and Breast Unit of ASST Spedali Civili Brescia from November 2017 to February 2023 were retrospectively evaluated. The main aim of the study was to evaluate clinical benefit rate (CBR) of the subsequent lines of therapy after CDK4/6i. Secondary aims were to report objective response rate (ORR) and progression-free survival (PFS). Median age was 60 years. CDK4/6i were administered as first-line therapy in 26.2%, as second-line in 40.3%, and as a third or further line in 33.5% of patients. After a median follow-up of 30.5 months, 126 patients (57%) experienced a disease progression and had a median PFS of 14.3 months: the most common sites of disease progression were liver (42%), bone (31.7%), and lungs (12%). A total of 112 patients received a further line of treatment: 13.4% received ET monotherapy (either fulvestrant or aromatase inhibitor), 13.4% ET plus target therapy (such as an mTOR inhibitor), 42% metronomic chemotherapy (CT), and 31.2% received intravenous CT (either anthracyclines, taxanes, eribulin, or other drugs). A higher CBR was noted in patients receiving metronomic CT, in comparison to intravenous CT and ET with or without target therapy (51.9% vs 31.5% vs 16.7%, respectively, p = 0.04). Median PFS after CDK4/6i was 9 months (5.93-12.06). Associations between ORR after CDK4/6i and patients’ clinical characteristics will be presented at the meeting. These single-center retrospective data suggest that CT, in particular metronomic CT, may show better favorable outcomes after progression on CDK4/6i. Evidence from prospective, randomized clinical trial is warranted.