Prediction of better clinical outcomes based on the development of neutropenia during the first course of trifluridine/tipiracil treatment for advanced/recurrent colorectal cancer

Trifluridine/tipiracil is a standard treatment after the third-line treatment for advanced/recurrent colorectal cancer (CRC). This study aimed to clarify whether trifluridine/tipiracil-induced neutropenia (degree and time of onset) is predictive of better clinical outcomes in patients with CRC. We retrospectively identified 130 patients who received trifluridine/tipiracil for treating CRC at Ogaki Municipal Hospital (Ogaki, Japan) between July 2014 and July 2021. Kaplan-Meier and log-rank tests and multivariate analysis were performed to evaluate overall survival (OS) according to the degree and time of onset of neutropenia. The median OS of patients who developed Grade 1-2 neutropenia (n=27) and those who developed Grade 3-4 neutropenia (n=51) was 185 days (95% confidence interval [CI]: 154-223) and 279 days (95% CI: 214-301), respectively (log-rank test, p=0.002). The median OS of patients who developed >_ Grade 3 neutropenia during the first course of treatment (n=25) and those who developed >_ Grade 3 neutropenia after the second course (n=26) was 300 days (95% CI: 246-458) and 211 days (95% CI: 173-299), respectively (log-rank test, p=0.137). Compared with that of patients who did not develop neutropenia, the hazard ratio for death of patients who developed neutropenia during the first course of treatment was 0.608 (95% CI, 0.385-0.958; p=0.032). Although the timing of severe neutropenia during trifluridine/tipiracil administration was not related to OS, the presence or absence of neutropenia during the first course of trifluridine/tipiracil administration can predict prolongation of OS in patients with CRC.