Risk Factors and Clinical Significance of Grade ≥3 Neutropenia During the First Cycle of Cabazitaxel Therapy With Primary Pegfilgrastim Prophylaxis in Metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Cabazitaxel is an established treatment for metastatic castration-resistant prostate cancer (mCRPC) previously treated with a docetaxel-containing regimen; however, it is frequently associated with severe neutropenia. Although primary prophylaxis with pegfilgrastim is widely used, severe neutropenia still occurs. The present study aimed to identify risk factors for grade ≥3 neutropenia during the first cabazitaxel cycle (Cycle 1) under universal pegfilgrastim prophylaxis and to evaluate its clinical significance. PATIENTS AND METHODS: This retrospective study analyzed 40 patients with mCRPC treated with cabazitaxel at our institution between January 2015 and January 2025. All patients received primary prophylactic pegfilgrastim on day 3 of each cycle. The primary endpoint was the occurrence of grade ≥3 neutropenia during Cycle 1. A logistic regression analysis was performed to identify associated factors. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and compared using the Log-rank test. RESULTS: Grade ≥3 neutropenia during Cycle 1 occurred in 18 patients (45.0%). A univariate analysis identified age ≥75 years and prior docetaxel exposure ≥9 cycles as significant risk factors for grade ≥3 neutropenia. In a multivariate analysis, prior docetaxel exposure ≥9 cycles was identified as an independent predictor. Febrile neutropenia occurred in six patients (15.0%) during Cycle 1. There were no significant differences in OS or PFS between patients with and without grade ≥3 neutropenia. CONCLUSION: Despite universal pegfilgrastim prophylaxis, severe neutropenia during the first cabazitaxel cycle remains common, particularly in patients with extensive prior docetaxel exposure. However, early grade ≥3 neutropenia was not associated with poorer survival outcomes. These results suggest that under adequate supportive care, early hematologic toxicity alone does not preclude continued cabazitaxel treatment.