202P Abemaciclib in HR+/Her2- Metastatic Breast Cancer Patients after Previous Progression on Palbociclib or Ribociclib: Clinical Experience in a Tertiary Hospital in Madrid, Spain

Preclinical and pharmacological data of the three approved cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) suggest differences among them. Abemaciclib inhibits other targets (CDK2/Cyclin A/E and CDK1/Cyclin B) causing cell cycle arrest in phases G1 and G2. In preclinical models, both senescence and apoptosis occurred earlier and at lower concentrations of Abemaciclib, compared to treatment with either palbociclib or ribociclib. Abemaciclib monotherapy or combined with tamoxifen has demonstrated activity in endocrine refractory metastatic breast cancer (MBC) who had received prior treatment with chemotherapy. There are limited clinical data of abemaciclib after a prior CDK4/6i exposure. To assess the safety profile and clinical outcomes of a consecutive cohort of HR+/HER2- MBC patients treated with abemaciclib beyond a previous progression on palbociclib or ribociclib at our institution. From April, 2020 until February, 2022, 11 women met inclusion criteria and were included. 9 out 11 received abemaciclib combined with tamoxifen. 8 patients had visceral involvement, none had brain metastasis. Median age was 69 years (range 42-84 years). Median time to abemaciclib from the end of previous CDK4/6i was 17.5 months (range 3-41 months). Median number of therapies until rechallenge was 3 (range 1-7) including chemotherapy in 54.5% of patients. Median time of follow-up was 6 months (range 1-22 months). The median progression-free survival (PFS) was 6 months (95%CI 3.5 – 10). 5 patients still continue on abemaciclib. Of these, 1 patient with hepatic metastases achieved complete response. Clinical benefit rate (CBR) at 24 weeks was seen in 5 patients out of 8 evaluable patients. Most common adverse events (AEs) were diarrhea (72.7%, no grade ≥ 3) and asthenia (27.3%, no grade ≥3). Neutropenia grade 4 was seen in a heavily treated patient with previous episodes on other therapies. Abemaciclib may result an effective and safe treatment option in MBC patients previously treated with palbociclib or ribociclib. Further prospective studies to confirm this hypothesis are required.