Use of CDK4/6 Inhibitors in the First-Line Treatment of HR+/HER2− Metastatic Breast Cancer: A Real-Life Experience in Morocco

Abstract

In troduction: Luminal/HER2− negative breast cancer represents approximately 70% of all breast cancers. Historically, endocrine therapy was the standard first-line treatment. Over the past two decades, major therapeutic advances, particularly the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy, have significantly improved progression-free survival (PFS) and overall survival (OS) in this population. Materi a l and Methods: We conducted a retrospective cohort study at the Department of Medical Oncology, Hassan II University Hospital, including 60 patients with HR+/HER2− metastatic breast cancer, either de novo or recurrent, who were treatment-naïve in the metastatic setting. All patients received a CDK4/6 inhibitor (palbociclib or ribociclib) in combination with endocrine therapy between January 2020 and June 2025. Clinical, histopathological, and therapeutic data were collected, and treatment response was assessed according to RECIST 1.1 criteria. Results: The median age was 53.3 years (range: 27 - 92), with 53% postmenopausal. A family history of cancer was reported in 8.3% of patients. Most patients had good performance status (WHO 0 - 1: 85%). The most common metastatic sites were bone (76.7%) and lymph nodes (58.3%). Palbociclib was used in 47% of patients, and ribociclib in 53%. Mean PFS was 33.0 months (95% CI: 22.2 - 43.7), while median OS was not reached at the time of analysis. Patients with hormone-sensitive disease or secondary resistance had significantly longer PFS than those with primary resistance (33.6 vs 3.5 months; p < 0.001). The main toxicities were hematologic, with grade 3 and 4 neutropenia occurring in 21.7% and 6.7% of patients, respectively. Conclusion: CDK4/6 inhibitors combined with endocrine therapy are effective and well-tolerated in the first-line management of HR+/HER2− metastatic breast cancer in a real-world Moroccan cohort, supporting their role as the current standard of care.