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J Clin Oncol. 2018 Feb 1;36(4):350-358. doi: 10.1200/JCO.2017.74.3245. Epub 2017 Dec 7.

Results of a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of Trifluridine/Tipiracil (TAS-102) Monotherapy in Asian Patients With Previously Treated Metastatic Colorectal Cancer: The TERRA Study.

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Jianming Xu, Affiliated Hospital Cancer Centre, Academy of Military Medical Sciences (The 307 Hospital Cancer Centre of People's Liberation Army); Lin Shen, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing; Hongming Pan, Sir Run Run Shaw Hospital Medical School, Zhejiang University, Hangzhou; Ruihua Xu, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou; Weijian Guo and Jin Li, Fudan University Shanghai Cancer Center; Tianshu Liu, Zhong Shan Hospital, Fudan University; Qi Li, Shanghai Jiaotong University affiliated First People's Hospital; Jin Li, Tongji University Affiliate Shanghai East Hospital, Shanghai; Chunmei Shi, Fujian Medical University Union Hospital, Fuzhou; Yuxian Bai, Third Affiliated Hospital of Harbin Medical University, Harbin; Feng Bi, West China Hospital, Sichuan University, Chengdu; Shukui Qin, Chinese People's Liberation Army Cancer Center of Nanjing Bayi Hospital, Nanjing; Changping Wu, The First People's Hospital of Changzhou, Changzhou; Dong Ma, Guangdong General Hospital, Guangzhou, Guangdong, China; Tae Won Kim, Asan Medical Center, University of Ulsan College of Medicine; Sae-Won Han, Seoul National University Hospital; Young Suk Park, Samsung Medical Center, Sungkyunkwan University School of Medicine; Joong Bae Ahn, Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University, College of Medicine, Seoul, Republic of Korea; Virote Sriuranpong, Chulalongkorn Hospital, Bangkok, Thailand; and Donghu Lin, Taiho Pharmaceutical, Tokyo, Japan.


Purpose Trifluridine/tipiracil (TAS-102) was effective in patients with metastatic colorectal cancer (mCRC) in a phase II Japanese trial. This regional trial evaluated the efficacy and safety of trifluridine/tipiracil in Asian patients with mCRC with or without exposure to biologic therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase III trial was conducted at 30 sites in China, the Republic of Korea, and Thailand. 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 were enrolled. Eligible patients were randomly assigned (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. The primary end point was overall survival (intent-to-treat population). Results Between October 16, 2013, and June 15, 2015, 406 patients were randomly assigned to receive trifluridine/tipiracil (n = 271) or placebo (n = 135). Risk of death was significantly lower in the trifluridine/tipiracil arm than in the placebo arm (hazard ratio for death, 0.79; 95% CI, 0.62 to 0.99; log-rank P = .035). Median overall survival was significantly longer in the trifluridine/tipiracil than in the placebo arm (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. The incidence of serious adverse events was similar between the arms (trifluridine/tipiracil, n = 63 [23.2%]; placebo, n = 32 [23.7%]). No treatment-related deaths were reported. Conclusion Trifluridine/tipiracil has a statistically significant survival benefit compared with placebo in Asian patients with mCRC refractory or intolerant to standard chemotherapies, regardless of exposure to biologic therapy. The safety profile is similar to previous reports.


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