Impact of renal impairment on chemotherapy-induced neutropenia in patients who are treated with trifluridine/thymidine phosphorylase inhibitor + bevacizumab for metastatic colorectal cancer

Although the phase III SUNLIGHT trial has demonstrated the survival benefit of the addition of bevacizumab (Bmab) to trifluridine/thymidine phosphorylase inhibitor (FTD/TPI), neutropenia, which frequently occurs during FDT/TPI + Bmab therapy, is a concern for clinicians. As TPI is excreted by the kidneys, the risk of adverse events is likely to be high in patients with an impaired renal function. This study aimed to investigate the relationship between renal impairment and the incidence of chemotherapy-induced neutropenia during FTD/TPI + Bmab therapy using real-world data. We retrospectively reviewed the medical records of 69 patients with metastatic colorectal cancer (mCRC) who were treated with FTD/TPI + Bmab for more than 28 days. Patients with renal impairment with an eGFR of 30–44 mL/min/1.73 m ² were defined as the G3b group. Seven patients (10.1%) were classified into the G3b group. Among the 69 patients enrolled in this study, grade ≥ 3 neutropenia was observed in 34 patients (49.3%), and grade 4 neutropenia was observed in 9 patients (13.0%). Patients in the G3b group had an approximately 24% higher incidence of grade ≥ 3 neutropenia in comparison to others (71.4% vs. 46.8%), and the incidence of grade 4 neutropenia in the G3b group was significantly higher than that in others (42.9% vs. 9.7%, p = 0.042). In an analysis limited to the G3b group, of the 5 patients who developed grade ≥ 3 neutropenia, four patients (80%) developed grade ≥ 3 neutropenia, and 2 (40%) developed grade 4 neutropenia within 30 days after initiation of FTD/TPI + Bmab therapy. However, the duration required for neutrophil count to recover to ≥ 1500 /mm ³ and the treatment effects of the G3b group were comparable to those observed in other patients. FTD/TPI + Bmab therapy is associated with a high risk of severe neutropenia within 30 days of initiation, especially in patients with a decreased renal function.