Impact of the CDK4/6 Inhibitor Line of Use on Progression-Free Survival in HR+/HER2? Metastatic Breast Cancer: Real-Life Experience in Morocco

Abstract

Author(s): Diango Keita*, Mehdi Alem, Mounir Belcadi, Abir Oufrid, Sara Nejjari, Lamiae Amaadour, Karima Oualla, Zineb Benbrahim, Samia Arifi and Nawfel Mellas

Introduction Hormone receptor–positive (HR+) and human epidermal growth factor receptor 2–negative (HER2−) metastatic breast cancer represents the most common molecular subtype. The introduction of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in combination with endocrine therapy has profoundly changed the therapeutic paradigm. However, real-world data from low- and middle-income countries remain limited, and the optimal timing for CDK4/6 inhibitor initiation is still debated, particularly following the publication of the SONIA trial. Methods We conducted a retrospective cohort study at the Department of Medical Oncology of Hassan II University Hospital in Fez. Forty-one patients with de novo or recurrent HR+/HER2− metastatic breast cancer treated with palbociclib or ribociclib in combination with endocrine therapy between January 2018 and December 2024 were included. CDK4/6 inhibitors were administered in either the first-line or second-line setting. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR, defined as partial response or stable disease ≥ 24 weeks), safety, and tolerability. Cox proportional hazards models were used for univariate and multivariate analyses of prognostic factors. Results The median age was 55.2 years (range, 31–92). CDK4/6 inhibitors were administered as first-line therapy in 63.4% of patients and as second-line therapy in 36.6%. The median progression-free survival was 29.2 months (95% CI: 23.5–34.9), while the median overall survival had not been reached at the time of analysis. A partial response was observed in 48.78% of patients, and the clinical benefit rate was high. Patients treated in the first-line setting showed a longer progression-free survival compared with those treated in the second line (29.2 vs. 10.4 months); however, this difference was not statistically significant (p = 0.248). Toxicities were mainly hematological, dominated by grade 3–4 neutropenia (58.5%). Conclusion In this real-world cohort, the combination of CDK4/6 inhibitors with endocrine therapy demonstrated meaningful clinical efficacy with manageable toxicity. Firstline use of CDK4/6 inhibitors may provide a relevant clinical benefit in resourcelimited settings. Further prospective studies adapted to local realities are needed to optimize therapeutic sequencing strategies.

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