Objective responses and survival outcomes by grade 3-4 neutropenia in refractory metastatic colorectal cancer treated with trifluridine/tipiracil: Real-world evidence from the ReTrITA study.

Abstract

e15611 Background: In refractory metastatic colorectal cancer (mCRC) treated with trifluridine/tipiracil (T), treatment-related neutropenia has been associated with improved survival. Whether this benefit is linked to objective response patterns in real-world practice remains unclear. This sub-analysis of the ReTrITA study evaluated survival outcomes according to objective response categories in patients stratified by grade 3-4 neutropenia. Methods: ReTrITA is a multicenter Italian real-world observational study including patients with refractory mCRC treated with T. Patients were stratified by the occurrence of grade 3/4 neutropenia (T neut vs T no-neut). Objective response was classified as partial response (PR), stable disease (SD), or progressive disease (PD). Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and compared across response categories using log-rank tests (χ²). Results: Overall, 843 patients were included in this substudy, of whom 807 (95.7%) were evaluable for objective response, including 265 in the T neut group and 542 in the T no-neut group. In the T neut group, PR, SD, and PD were observed in 5.9% (n = 16), 28.8% (n = 76), and 63.1% (n = 167) of patients, respectively. Overall survival differed significantly across response categories (log-rank χ² = 57.08, df = 2; p < 0.0001), with median OS of 21.7 months for PR, 20.9 months for SD, and 8.5 months for PD. Progression-free survival showed a similar gradient (log-rank χ² = 82.83, df = 2; p < 0.0001), with median PFS of 10.5, 8.5, and 3.7 months, respectively. In the T no-neut group, PR, SD, and PD were documented in 1.0% (n = 5), 20.3% (n = 110), and 73.4% (n = 398) of patients, respectively. Median OS was 13.0 months for PR, 15.5 months for SD, and 6.5 months for PD, with significant separation of survival curves (log-rank χ² = 75.66, df = 2; p < 0.0001). Median PFS was 7.2, 7.1, and 3.0 months, respectively (log-rank χ² = 119.74, df = 2; p < 0.0001). Across corresponding response categories, patients who developed grade 3–4 neutropenia consistently experienced longer OS and PFS compared with those without neutropenia. Conclusions: In this large real-world cohort of patients with refractory mCRC treated with T, objective response categories were strongly associated with OS and PFS. The occurrence of grade 3–4 neutropenia identified patients with consistently improved survival across response strata, supporting its role as a prognostic and pharmacodynamic marker of treatment benefit beyond radiological response.