Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors

This multicenter retrospective study assessed the safety and efficacy of trifluridine/tipiracil in the real-world setting in patients with chemotherapy refractory metastatic colorectal cancer (mCRC), while identifying predictive and prognostic clinicopathological factors. Our findings suggest that real-world safety and efficacy of trifluridine/tipiracil are in keeping with the pivotal clinical trial outcomes. Pretreatment neutrophil to lymphocyte ratio (NLR) and carcinoembryonic antigen (CEA) were prognostic, while treatment-induced grade 3 neutropenia was predictive for response. Background: The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study. Patient and methods: We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom. Results: A total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidinebased chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG >= 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P <=.001) and predictive value (OR: 4.1 and 6.7, P<.05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P<.001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy. Conclusion: Triflur idine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed. (C) 2021 Elsevier Inc. All rights reserved.