Xu J, et al. - In a phase II Japanese trial, trifluridine/tipiracil (TAS-102) showed efficacy in patients with metastatic colorectal cancer (mCRC). Researchers undertook this regional trial to assess the efficacy and safety of trifluridine/tipiracil in Asian patients with mCRC with or without exposure to biologic therapy. They found that regardless of exposure to biologic therapy, trifluridine/tipiracil vs placebo afforded a statistically significant survival benefit in Asian patients with mCRC refractory or intolerant to standard chemotherapies. Regarding safety profile, the results were similar to previous reports.

• Researchers performed this randomized, double-blind, placebo-controlled, phase III trial at 30 sites in China, the Republic of Korea, and Thailand.
• This study included patients ≥ 18 years old with histologically or cytologically confirmed adenocarcinoma of the colon or rectum and known KRAS status who were refractory or intolerant to two or more prior chemotherapy regimens.
• Random allocation of eligible patients (2:1 ratio; minimization method) to receive trifluridine/tipiracil (twice per day orally; 5 days on and 2 days off for 2 weeks, followed by 14 days off per cycle) or placebo, was done.
• Overall survival (intent-to-treat population) was the primary end point.

• A total of 406 patients were randomly assigned to receive trifluridine/tipiracil (n = 271) or placebo (n = 135) between October 16, 2013, and June 15, 2015.
• Researchers found significantly lower risk of death in the trifluridine/tipiracil arm as compared with the placebo arm (hazard ratio for death, 0.79; 95% CI, 0.62 to 0.99; log-rank P=.035).
• They noted that in the trifluridine/tipiracil vs in the placebo arm, median overall survival was significantly longer (7.8 months [95% CI, 7.1 to 8.8 months] v 7.1 months [95% CI, 5.9 to 8.2 months], respectively), for a median survival follow-up time of 13.8 months (95% CI, 13.1 to 15.3 months) compared with 13.4 months (95% CI, 11.6 to 17.3 months), respectively.
• Findings demonstrated similar incidence of serious adverse events between the arms (trifluridine/tipiracil, n = 63 [23.2%]; placebo, n = 32 [23.7%]).
• In addition, no treatment-related deaths were reported.