Prognostic factors in refractory metastatic colorectal cancer patients treated with Trifluridine/Tipiracil

PURPOSE: The systemic treatment options for metastatic colorectal cancer (mCRC) are unsatisfactory, and the disease recurs despite the use of numerous medications and their combinations. Trifluridine/Tipiracil is a relatively new drug used in refractory mCRC. Little is known about its real-world effectiveness and prognostic and predictive factors. Therefore, this study aimed to develop a prognostic model for refractory mCRC treated with Trifluridine/Tipiracil. METHODS: We retrospectively evaluated the data from 163 patients who had received Trifluridine/Tipiracil as a third or fourth line of treatment for refractory mCRC. RESULTS: After starting Trifluridine/Tipiracil, 21.5% of patients survived one year, and the median overall survival after Trifluridine/Tipiracil initiation was 251 days (SD: 17.855; 95%CI: 216–286). Median progression-free survival after Trifluridine/Tipiracil initiation was 56 days (SD: 4.826; 95%CI 47–65). Moreover, the median overall survival from diagnosis was 1333 days (SD: 82.84; 95%CI: 1170–1495). In forward stepwise multivariate Cox regression analysis, initial radical treatment (HR = 0.552, 95% CI 0.372–0.819, p < 0.003), the number of cycles of first-line chemotherapy (HR = 0.978, 95% CI 0.961–0.995, p < 0.011), the number of cycles of second-line chemotherapy (HR = 0.955, 95% CI 0.931–0.98, p < 0.011), BRAF mutation (HR = 3.016, 95% CI = 1.207–7.537, p = 0.018), and hypertension (HR = 0.64, 95% CI = 0.44–0.931, p = 0.02) were all associated with survival after Trifluridine/Tipiracil initiation. Our model and model-based nomogram displayed an AUC of 0.623 for one-year survival estimation in the testing cohort. The C-index for the prediction nomogram was 0.632. CONCLUSION: We have developed a prognostic model for refractory mCRC treated with Trifluridine/Tipiracil based on five variables. Moreover, we reported a nomogram which could be used by oncologists in clinic visits on a daily basis. GRAPHICAL ABSTRACT: [Image: see text]