The introduction in clinical practice of selective cyclin-dependent kinase 4/6 inhibitors(CDK4/6i) improves the outcome of patients with hormone receptor-positive ( HR+) human epidermal growth factor 2 negative(HER-2) advanced/metastatic breast cancer (a/mBC). 

The aim of the study was to demonstrate the safety and effectiveness of the use of CDK4/6i in patients with HR+/HER2- a/mBC in Cyprus by comparing the results with data derived from randomized clinical trials (RCTs) and real-world data studies( RWDs). According to methology, a retrospective analysis of data from 269 patients with confirmed HR+/HER2-a/mBC treated with endocrine therapy (ET) in combination with palbociclib or ribociclib or abemaciclib as first or second or third line of treatment in the bank of Cyprus Oncology center (BOCOC) from 2018 to 2021. Seventy patients from the retrospective study who continued to receive treatment with CDK4/6i containing regimens from 2021, participated in the prospective study (follow-up period 2021-2023). A statistical analysis was performed using the statistical computer language R(v4.3.1). In terms of retrospective results, 269 patients were treated with CDK4/6i (149 palbociclib, 103 ribociclib, 17 abemaciclib). The majority of patients received CDK 4/6i in the first line (68%, n=182/269) and 25% and 7.8 % of patients received  CDK 4/6i as second and third line of treatment respectively. The median progression free survival(mPFS) was 31.25 and 19 months for palbociclib, ribociclib and abemaciclib respectively. The media overall survival (mOS) was 60.54 and 44 months for palbociclib,  ribociclib and abemaciclib respectively. Neutropenia was the most common reportedadverse events( AE) in 40.1% patients, followed by diarrhea (27.6%), ALT/AST increase (13.4 %), pneumonia (8.2), thrombocytopenia (4.8%), erythematous rash (3.3%), pro;pgned QT interval (1.9%) patients. According to prospective results, 70 patients were treated with CDK4/6i ( 29 palbociclib, 31 ribociclib, 10 abemaciclib). The majority of patients received CDK 4/6i in the first line ( 37%, n =26/70) and 39% and 24% of patients received CDK4/6i as second and third line of treatment respectively. The mPFS was 31.25 and 16.5 months for palbociclib, ribociclib, abemaciclib respectively. Diarthea was the most common AE reported in 35.3 % patients, followed by neutropenia (29.3%), ALT/AST increase (19.9%), prolonged QT interval (8.6%), pneumonia (4.3%), and thrombocytopenia (1.4%).

Conclusively, according to subgroup analysis for both retrospective study, age 65 years, the higher BC grade, de novo metastatic stage IV at initial diagnosis, presence of lymph node/ liver metastasis/brain metastasis at time of CDK4/6i treatment, the larger number of metastatic sites at time of CDK4/6i treatment, the use of CDK4/6i in a later line of treatment, were  associated  with a significantly shorter PFS and they were negative prognostic factors for effectiveness of CDK 4/6i administration. The combination of CDK 4/6i with ET is the golden standard treatment in HR+HER2- a/mBC, bringing a prolongation of survival for patients. The results show no major differences compared to RCTs and other RWD and confirm the effectiveness and tolerability of CDK 4/6i in clinical practice routine. This is the first RWD describing and comparing the effectiveness and toxicity of three CDK 4/6i in Cyprus population.