Trifluridine/Tipiracil Improves Survival in Patients with Metastatic Colorectal Cancer

Oral trifluridine/tipiracil hydrochloride may be a new treatment option in Asia in the third-line and higher setting in mCRC

The anticancer agents trifluridine and tipiracil hydrochloride (trifluridine/tipiracil) combined in tablet formulation that can be taken orally demonstrated significant improvements in overall survival (OS) and progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC), according to a subgroup analysis of data from 3 Asian countries presented at the ESMO Asia 2017 in Singapore, an Annual Congress organised by the European Society for Medical Oncology.

Virote Sriuranpong, Medicine, Chulalongkorn University Faculty of Medicine, Bangkok, Thailand, discussed findings from an analysis of data according to country-based subgroups in the TERRA study (NCT01955837) comparing the efficacy and safety of combined trifluridine/tipiracil with placebo in Asian patients with mCRC. Trifluridine is a nucleoside analogue and tipiracil hydrochloride inhibits thymidine phosphorylase.

TERRA enrolled patients from centres in China, the Republic of Korea, and Thailand who had received at least 2 prior standard regimens for mCRC including fluoropyrimidines, oxaliplatin and irinotecan. Eligible patients were randomized 2:1 to receive oral tablets of trifluridine/tipiracil hydrochloride at 35 mg/m2 twice daily for a 5 days on and 2 days off schedule for 2 weeks, followed by 14 days off per cycle, or placebo in each country.

Of the 406 randomised patients, 305 (75.1%) were from China, 81 (20.0%) from the Republic of Korea, and 20 (4.9%) patients comprised the Thailand subgroup.

Survival benefits observed with trifluridine/tipiracil hydrochloride in each country

Improved survival was observed in patients overall and across all 3 country subgroups with trifluridine/tipiracil.

In the Chinese subgroup, improved OS and PFS, hazard ratio [HR] 0.82 (95% confidence interval 0.62,1.08), and HR 0.41 (95% CI 0.31, 0.54) were observed in the 204 patients receiving trifluridine/tipiracil compared to 101 patients on placebo, respectively.

The subgroup of 55 patients treated with trifluridine/tipiracil from the Republic of Korea also showed improved OS and PFS compared to the 26 patients on placebo, HR 0.77 (95% CI 0.48, 1.26) and HR 0.56 (95% CI 0.34, 0.93), respectively.

The 12 patients in the Thailand subgroup on trifluridine/tipiracil showed improved OS and PFS compared to the 8 patients on placebo, HR 0.54 (95% CI 0.19, 1.53) and HR 0.54 (95% CI 0.20, 1.42), respectively.

Trifluridine/Tipiracil Improves Survival in Patients with Metastatic Colorectal Cancer

Overview of OS and PFS by Country


The most commonly reported grade ≥3 adverse events according to NCI-CTCAE version 4.0 across all 3 countries were haematological adverse events; more than 30% of patients in each country receiving trifluridine/tipiracil hydrochloride reported grade 3 or higher neutropenia. No cases of febrile neutropenia was reported and the incidence was less than 2% of grade ≥3 treatment emergent adverse events, including nausea, vomiting and diarrhoea in patients receiving trifluridine/tipiracil per country.


The overall and progression-free survival benefits observed with trifluridine/tipiracil in each Asian country analysed support the potential of this oral agent as a new option for third-line or later treatments for patients with mCRC in Asia.

The authors noted that the safety profile of trifluridine/tipiracil in the TERRA trial was similar to previously reported safety profiles.


This study was sponsored by Taiho Pharmaceutical Co., Ltd.


142O - Sriuranpong V, et al. Phase III study of Trifluridine/tipiracil versus placebo in Asian patients with metastatic colorectal cancer (TERRA study): country subgroup.