Relationship Between Thymidine Kinase 1 Expression and Trifluridine/Tipiracil Therapy in Refractory Metastatic Colorectal Cancer: A Pooled Analysis of 2 Randomized Clinical Trials

No predictive biomarker to indicate the clinical benefit of trifluridine/tipiracil (FTD/TPI) has been identified. Individual patient data from 329 patients from 2 randomized placebo-controlled trials were analyzed to determine the relationship between thymidine kinase 1 (TK1) expression and FTD/TPI efficacy in refractory metastatic colorectal cancer. Patients with high TK1 expression showed an improvement in overall survival when treated with FTD/TPI. Background: High thymidine kinase 1 (TK1) activity increases the incorporation of trifluridine (FTD) into DNA; thus, D antitumor activity is likely to increase in patients with high tumoral TM activity. To date, no established predictive biomarker to indicate the clinical benefit of FTD/tipiracil (TPI) has been identified. We aimed to determine the relaionship between TK1 expression and FTD/TPI efficacy in refractory metastatic colorectal cancer. Patients and Methods: Individual patient data from 2 randomized placebo-controlled trials were analyzed. We measured TK1 protein expression in tumor tissue samples and its relationship with FTD/TPI clinical efficacy using overall survival (OS), progression-free survival, and disease control rate. Results: This study comprised 329 patients (FTD/TPI, 224; placebo, 105). FTD/TPI significantly improved OS versus placebo in the high-expression (cutoff > 15%) TK1 group (median OS, 7.8 vs. 6.8 months; hazard ratio - 0.65; 95% confidence interval, 0.46-0.93; P = .018). The low-expression (cutoff < 15%) TK1 group experienced a smaller OS benefit (9.3 vs. 7.4 months; hazard ratio - 0.88; 95% confidence interval, 0.63-1.23; P = .45). For patients who received placebo, the high-expression TK1 group had a slightly worse prognosis than the low-expression TK1 group. The tendency of FTD/TPI efficacy concerning progression-free survival and disease control rate was not similar to that concerning OS between groups. Conclusion: Patients with high TK1 expression showed an improvement in OS when treated with FTD/TPI. Further investigations are warranted to confirm this relationship. (C) 2018 The Authors. Published by Elsevier Inc.