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

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.

Effectiveness, safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real‐world data from the noninterventional TACTIC study in Germany

“…Interestingly, in contrast to the data reported in the pivotal RECOURSE trial, where no differences were observed between age subgroups (7.1 months in patients <70 years vs 7.0 months in patients ≥70 years), in TACTIC there was a slight OS benefit observed in older patients (8.6 months) as compared to young and intermediate age patients (7.4 and 6.8 months, respectively) 9 . These findings suggest that low metastatic burden and indolent disease as well as older age may be considered not only as favorable prognostic factors but also as predictive factors for survival and preservation of ECOG PS in patients with pretreated mCRC receiving FTD/TPI in routine clinical practice, bearing in mind the limited comparability between real‐world and clinical trial data as reported previously 26,27 . Moreover, patients with BPC or GPC may maintain a good general condition and performance status for a longer period of time as compared to patients with PPC.…”

Biomarkers of Trifluridine-Tipiracil Efficacy

“…In a cohort of 379 metastatic colorectal cancer patients who received trifluridine/tipiracil mostly as a third or later-line treatment in the Spanish multicenter ROS study, the median OS was 7.9 months [ 35 ]. Patients with a maximum of two metastatic sites, without liver metastases, with alkaline phosphatase less than 300 IU and with a neutrophil-to-lymphocyte ratio of less than five had a significantly longer OS than patients with three or more metastatic sites, liver metastases, alkaline phosphatase levels above 300 IU and a neutrophil-to-lymphocyte ratio above five [ 35 ].…”

“…Grade 2 and higher neutropenia and higher CEA levels were independent prognostic factors for OS. Patients in the ROS study who had trifluridine/tipiracil dose reductions, presumably due to neutropenia, had a longer OS than that of patients who did not need a dose reduction [ 35 ].…”

“…As mentioned above, two peripheral blood laboratory values, the neutrophil-to-lymphocyte ratio and alkaline phosphatase, together with two clinical factors, the number of metastatic sites and the presence of liver metastases, were prognostic for trifluridine/tipiracil efficacy in the ROS cohort [ 35 ]. In another small retrospective series of 33 metastatic colorectal cancers treated with trifluridine/tipiracil, patients with neutrophil-to-lymphocyte ratios above five before start of treatment had significantly worse OS and PFS rates than those of their counterparts with neutrophil-to-lymphocyte ratios below five [ 42 ].…”

Explore the Predictive Value of Peripheral Blood Cell Parameters in Refractory Mycoplasma pneumoniae Pneumonia in Children Over 6 Years Old

“…Lattanzi et al found that NLR was associated with 30-day mortality and morbidity after intracerebral hemorrhage, which could improve outcome prediction of acute intracerebral hemorrhage (11). They also played an important role in the prognosis of acute ischemic stroke patients undergoing revascularization treatment (12,13), and had a certain predictive value in the occurrence, efficacy, and prognosis of tumors (14)(15)(16). The above evidence shows the significance and broad potential of serum biomarkers that are easy to obtain and inexpensive in daily clinical practice.…”