Effect of thymidine kinase 1 expression on prognosis and treatment outcomes in refractory metastatic colorectal cancer: Results from two randomized studies of TAS-102 versus a placebo.

Abstract

529 Background: TAS-102 is an oral nucleoside antitumor agent, comprising trifluridine (FTD) and tipiracil. FTD is incorporated into DNA after phosphorylation by thymidine kinase 1 (TK1). This study aimed to investigate the association between TK1 expression and TAS-102 efficacy in refractory metastatic colorectal cancer (mCRC) patients (pts). Methods: Data from two randomized phase 2 and phase 3 studies of mCRC pts refractory to standard therapies were analyzed for treatment outcomes in relation to TK1 expression. Expression was measured using immunohistochemistry, and staining was classified according to intensity and scored 0, 1+, 2+, or 3+. Occupancy rates of the areas scored 2+ and 3+ in tumor cells were calculated in 5% intervals, and divided into two groups (high or low TK1) at each cut-off point. Results: TK1 expression was evaluated in 329 pts. Baseline characteristics and treatment outcomes were comparable between the TK1-refined and intention-to-treat populations. Pts with high TK1 expression who received the placebo had a poor prognosis, while those receiving TAS-102 showed a significant improvement in overall survival (OS) at cut-off points of 5% to 15%, and 30%. Conclusions: High TK1 expression could be a poor prognostic factor and a predictive factor of TAS-102 efficacy in mCRC pts. [Table: see text]