Impact of TAS‑102 dose reduction on severe neutropenia and survival outcomes in patients with metastatic colorectal cancer and prior chemotherapy‑induced neutropenia

The present study aimed to evaluate the impact of initial dose reduction of trifluridine/tipiracil (TAS-102) monotherapy on the incidence of severe neutropenia and overall survival (OS) in individuals with metastatic colorectal cancer, considering prior chemotherapy-induced severe neutropenia. Participants were classified into the following three groups: A group, individuals who did not experience severe neutropenia during previous chemotherapy and did not undergo dose reduction (n=61); B1 group, those who experienced severe neutropenia during previous chemotherapy and received an initial dose reduction of TAS-102 (n=28); and B2 group, those who experienced severe neutropenia but did not receive a dose reduction (n=88). Neutropenia severity, progression-free survival (PFS) and OS were compared among the groups. Notably, there was no significant difference in the incidence of grade 3 or higher neutropenia among the three groups during TAS-102 administration (P=0.958). The median OS times in the A group (n=61), B1 group (n=28) and B2 group (n=88) were 273 days (95% CI, 199-299), 285 days (95% CI, 202-NA) and 233 days (95% CI, 182-272), respectively (log-rank test, P=0.165). The median PFS times among the three groups were 133.0 days (95% CI, 98-153), 94.5 days (95% CI, 77-133) and 93.5 days (95% CI, 83-100), respectively (log-rank test, P=0.053). In conclusion, a proactive dose reduction at TAS-102 treatment initiation based on pre-existing severe neutropenia should be carefully considered, as it may not be necessary.