Final survival results of a multicenter phase I/II study of TAS-102 with bevacizumab for mCRC (C-TASK FORCE)

Abstract

Background: The concentration of phosphorylated trifluridine (FTD) in tumors was higher in TAS‐102 with bevacizumab than in TAS102 monotherapy in preclinical model, resulting in enhanced activity of the combination against colorectal cancer cells compared with either drug alone. Clinical efficacy was demonstrated by the phase I/II study which showed centrally‐assessed progressionfree survival (PFS) rate at 16 weeks as was 42.9%, and median PFS by investigator assessment was 5.6 months in patients (pts) with mCRC. Methods: Eligibility criteria were mCRC pts who were refractory or intolerant to all standard therapies without regorafenib. Data cutoff was 29 Jan 2016. Here, we report the final results of a prespecified analysis of survival outcomes by RAS status, 26 cancerrelated actionable gene mutations using Next Generation Sequencing (NGS) and thymidine kinase 1 (TK1) immunohistochemical expression and a post hoc analysis of survival outcomes by chemotherapy‐induced neutropenia (CIN) in the first cycle. Results: From February to July 2014, 25 pts were enrolled and received TAS‐102 (35 mg/m2 BID on day 1‐5 and 8‐12 q4w) with bevacizumab (5 mg/kg q2w). Median overall survival (OS) was 11.4 months. There was no statistically significant difference in PFS and OS between pts with wild‐type RAS and mutant. Any mutation identified by NGS as well as TK‐1 expression level was not associated with survival outcomes. Pts who developed grade 2 CIN in the first cycle had a longer PFS compared to pts who did not (median, 5.8 months versus 1.9 months;Log‐rank P‐value = 0.0006), as well as OS (median, 12.7 versus 5.2 months; Log‐rank P‐value<0.0001). Conclusions: TAS‐102 with bevacizumab showed a promising antitumor activity and seemed more effective than TAS‐102 monotherapy irrespective of RAS status, known actionable mutations and TK‐1 expression. The CIN in the first cycle was statistically significantly associated with survival outcomes.