On-Treatment Grade 3-4 Neutropenia and Clinical Outcomes with Trifluridine/Tipiracil in Refractory Metastatic...

Background: Trifluridine/tipiracil (T) is a standard treatment for refractory metastatic colorectal cancer (mCRC). In randomized trials, treatment-emergent neutropenia has been associated with improved outcomes, suggesting a potential link with drug activity. However, evidence from routine clinical practice remains limited. This sub-analysis of the multicenter ReTrITA study evaluated the association between severe neutropenia and clinical outcomes in a real-world setting. Methods: Patients with refractory mCRC treated with T within the ReTrITA cohort were included. Patients were stratified according to the occurrence of grade 3-4 neutropenia. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox models. Results: Among 843 patients, 271 (32.1%) developed grade 3-4 neutropenia. The occurrence of severe neutropenia was significantly associated with improved survival outcomes. Median OS was 10.9 months versus 7.6 months, HR 0.64; 95% CI, 0.55-0.75; p < 0.0001), and median PFS was 4.3 months versus 3.3 months (HR 0.63; 95% CI, 0.55-0.73; p < 0.0001) in patients with versus without neutropenia, respectively. Conclusions: In this large real-world cohort, grade 3-4 neutropenia during T treatment was associated with significantly improved OS and PFS, supporting its role as a potential on-treatment prognostic marker. Prospective studies are warranted to confirm these findings.