Efficacy and Safety of Cyclin-Dependent Kinase 4/6 Inhibitor in Patients with Advanced Breast Cancer: A Real-World Experience

Background: CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) represent the standard of care for HR+/HER2- metastatic breast cancer (MBC). Real-world evidence (RWE) is essential to evaluate their effectiveness and safety in routine practice. This study describes the initial experience with CDK4/6i within the Medical Oncology Department of the Moulay Ismail Military Hospital in Meknes, Morocco. Methods: A retrospective observational cohort study was conducted on 30 patients with HR+/HER2- MBC, followed between January 2020 and December 2024, and treated with palbociclib (n=13) or ribociclib (n=17) in combination with ET. Clinicopathological, therapeutic, early response, safety (graded according to CTCAE v5.0), dose reduction, and temporary interruption data were collected and descriptively analyzed. Results: The mean patient age was 56.5 years; 36.7% (n=11) were premenopausal. Disease was de novo metastatic in 76.7% of patients, and 86.7% had ≥3 metastatic sites. CDK4/6i were predominantly used in the first line (83.3%), with a slight predominance of ribociclib (56.7%) over palbociclib (43.3%), mainly combined with letrozole (80%). The mean number of cycles received per patient was 9.53. Safety management required frequent adjustments: dose reductions occurred in 76.9% (10/13) of patients on palbociclib and 52.9% (9/17) on ribociclib. Temporary treatment interruptions were necessary for 76.9% (10/13) of patients on palbociclib and 52.9% (9/17) on ribociclib. Median progression-free survival (PFS), estimated using the Kaplan-Meier method, was 64 weeks. The most frequent adverse events (AEs) were hematological, notably Grade 3-4 neutropenia (Palbociclib 53.8%, Ribociclib 47.1%) and febrile neutropenia (Palbociclib 7.7%, Ribociclib 5.9%). Anemia and thrombocytopenia were common but mostly Grade 1-2. Fatigue (mainly Grade 1-2) was also common. Specific AEs noted with ribociclib included Grade 1-2 QT interval prolongation (11.8%), Grade 1-2 deep vein thromb