Trifluridine/tipiracil in metastatic colorectal cancer:An updated multicentre real-world analysis on efficacy, safety and predictive factors

BackgroundThe orally administered combination trifluridine and tipiracil hydrochloride (TAS-102) has been approved as third line treatment in metastatic colorectal cancer, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study.MethodsWe performed an updated multicentre retrospective observational study of patients with metastatic colorectal cancer, receiving TAS-102 as third line treatment between 2016 and 2019 in 8 cancer centers across the UK. Medical records were reviewed for clinicopathological characteristics, treatment, survival and toxicity outcomes. Prognostic and predictive factors were identified with uni-and multivariate regression analyses.ResultsA total of 236 patients were included. Median age was 69 years (31-89). All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG > 2. Median duration of TAS-102 treatment was 3 months (0.2-25.9), with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 months (95%CI 6.5-8.6) and median PFS 3.3 months (95%CI 3.01-3.57). A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. Neutropenia was present in 53%, (>G3 34%) with 4.6% cases of neutropaenic fever. Thrombocytopenia was less frequent 11% (>G3 1.6%). Fatigue was reported in 67.3% (G3 9%), nausea 30% (G3 3.3%) and diarrhoea 24.5% (G3 2%). Baseline Neutrophil to Lymphocyte ratio (NLR) <5 and CEA <200 had favourable prognostic (HR: 0.52 and 0.39, p < 0.001) and predictive value (OR: 4.1 and 6.7, p < 0.05). Development of G3 neutropenia predicted treatment response (OR: 0.32, p < 0.001). Following TAS-102 treatment 41% were referred for Phase I trial or rechallenged with chemotherapy.ConclusionsThese results are consistent with the efficacy and toxicity outcomes from RECOURSE study. However, lower disease control rates and higher rates of dose reductions are seen in the real-world population. Pre-treatment NLR and CEA could serve as potential markers for patient selection. Prospective validation is needed