TY  - EJOU
AU  - Signorelli, Carlo 
AU  - Basso, Michele 
AU  - Anghelone, Annunziato 
AU  - Calegari, Maria Alessandra 
AU  - Passardi, Alessandro 
AU  - Gallio, Chiara 
AU  - Bittoni, Alessandro 
AU  - Lucchetti, Jessica 
AU  - Angotti, Lorenzo 
AU  - Giacomo, Emanuela Di 
AU  - Zurlo, Ina Valeria 
AU  - Morelli, Cristina 
AU  - Dell’Aquila, Emanuela 
AU  - Artemi, Adele 
AU  - Gemma, Donatello 
AU  - Corsi, Domenico Cristiano 
AU  - Emiliani, Alessandra 
AU  - Ribelli, Marta 
AU  - Mazzuca, Federica 
AU  - Arrivi, Giulia 
AU  - Zoratto, Federica 
AU  - Morandi, Maria Grazia 
AU  - Santamaria, Fiorenza 
AU  - Dettori, Manuela 
AU  - Cosimati, Antonella 
AU  - Saltarelli, Rosa 
AU  - Minelli, Alessandro 
AU  - Lucci-Cordisco, Emanuela 
AU  - Chilelli, Mario Giovanni 

TI  - On-Treatment Grade 3–4 Neutropenia and Clinical Outcomes with Trifluridine/Tipiracil in Refractory Metastatic Colorectal Cancer: ReTrITA Real-World Evidence
T2  - Oncology Research

PY  - 2026
VL  - 34
IS  - 9
SN  - 1555-3906

AB  - <b>Background</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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; <i>p</i> &lt; 0.0001), and median PFS was 4.3 months versus 3.3 months (HR 0.63; 95% CI, 0.55–0.73; <i>p</i> &lt; 0.0001) in patients with versus without neutropenia, respectively. <b>Conclusions</b>: 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.
KW  - Trifluridine/tipiracil; metastatic colorectal cancer; neutropenia; real-world evidence; survival outcomes; prognostic biomarkers

DO  - 10.32604/or.2026.080964