Clinical and Biological Predictors of Severe Palbociclib- Induced Neutropenia in Patients with Hormone Receptor-Positive/HER2-Negative Metastatic Breast Cancer: A Retrospective Single-Center Study

Abstract

Background: Palbociclib, a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, is a standard treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) metastatic breast cancer. However, severe neutropenia remains its most common dose-limiting toxicity. This study aimed to determine the incidence and identify independent predictors of grade ≥3 palbociclib-induced neutropenia in a Moroccan real-world cohort. Methods: This retrospective single-center study included consecutive women with HR+/HER2− metastatic breast cancer treated with palbociclib plus endocrine therapy at the Mohammed VI Center for Cancer Treatment, Casablanca, Morocco, between May and December 2023. The primary endpoint was grade ≥3 neutropenia during the first three treatment cycles. Univariate and multivariable binary logistic regression analyses were performed to identify independent predictors. Results: A total of 65 patients were included. Grade ≥3 neutropenia occurred in 36 patients (55.4%), including grade 3 in 29 (44.6%) and grade 4 in 7 (10.8%). No cases of febrile neutropenia or permanent treatment discontinuation were observed. Most severe neutropenia occurred during the first treatment cycle (77.8%). Multivariable analysis identified age ≥56 years (adjusted OR, 29.15; 95% CI, 3.29–258.57; P=0.002), baseline ANC <2000/mm3 (adjusted OR, 20.25; 95% CI, 2.26–181.31; P=0.007), and WHO step III analgesic use (adjusted OR, 4.85; 95% CI, 1.17–20.10; P=0.030) as independent predictors. Conclusions: Grade ≥3 neutropenia was the most frequent clinically relevant toxicity associated with palbociclib. Older age, low baseline ANC, and WHO step III analgesic use independently predicted severe neutropenia. These findings may help identify patients who require closer hematological monitoring during the early phase of palbociclib treatment. List of Abbreviations: ANC – Absolute neutrophil count; BMI – Body mass index; CDK4/6 – Cyclin-dependent kinase 4 and 6; CI – Confidence interval; CTCAE – Common Terminology Criteria for Adverse Events; ECOG-PS – Eastern Cooperative Oncology Group Performance Status; HER2 – Human epidermal growth factor receptor 2; HR+ – Hormone receptor-positive; HR+/HER2− – Hormone receptor-positive/HER2-negative; IQR – Interquartile range; NCI – National Cancer Institute; OR – Odds ratio; SD – Standard deviation; WHO – World Health Organization.