Early Clinical Experience with Trifluridine/Tipiracil for Refractory Metastatic Colorectal Cancer: The ROS Study

SIMPLE SUMMARY: Trifluridine/tipiracil is an oral combination therapy currently approved as a salvage-line treatment in patients with metastatic colorectal cancer refractory to, or not, candidates for available therapies. However, there is no consensus on the specific factors that should be considered to select patients who benefit the most from trifluridine/tipiracil in clinical practice. The aim of our retrospective cohort study was to assess the early clinical experience with trifluridine/tipiracil in Spain and identify potential survival markers. Our findings endorse the real-life efficacy and safety of trifluridine/tipiracil for refractory metastatic colorectal cancer, as well as revealing the presence of ≤2 metastatic sites, absence of liver metastasis, alkaline phosphatase levels < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5 as survival markers. Combinations of these markers may help physicians to identify subsets of patients with refractory metastatic colorectal cancer that may benefit the most from trifluridine/tipiracil in their daily practice. ABSTRACT: Trifluridine/tipiracil is currently approved for metastatic colorectal cancer (mCRC) refractory to available therapies. However, there is no consensus on factors that predict treatment outcomes in daily practice. We assessed the early clinical experience with trifluridine/tipiracil in Spain and potential survival markers. This was a retrospective cohort study of mCRC patients who participated in the trifluridine/tipiracil early clinical experience programme in Spain. The primary outcome was overall survival (OS). Associations between OS and patient characteristics were assessed using multivariate Cox regression analyses. A total of 379 patients were included in the study. Trifluridine/tipiracil was administered for a median of 3.0 cycles and discontinued mainly due to disease progression (79.2%). The median OS was 7.9 months, with a 12-month OS rate of 30.5%. Cox analyses revealed that the following variables independently enhanced OS: ≤2 metastatic sites, no liver metastasis, alkaline phosphatase < 300 IU, trifluridine/tipiracil dose reductions, and neutrophil/lymphocyte ratio < 5. Grade ≥ 3 toxicities were reported in 141 (37.2%) patients, including mainly afebrile neutropaenia (23.2%), anaemia (12.1%), and thrombocytopaenia (5.3%). This study supports the real-life efficacy and safety of trifluridine/tipiracil for refractory mCRC and identifies tumour burden, liver metastasis, alkaline phosphatase, dose reductions, and neutrophil/lymphocyte ratio as survival markers.