Phase III study of trifluridine/tipiracil versus placebo in Asian patients with metastatic colorectal cancer (TERRA study): Country subgroup

Abstract

Background: Trifluridine/tipiracil is combination of trifluridine (FTD) and tipiracil hydrochloride (TPI) administered as an oral tablet. The TERRA study compared efficacy and safety of FTD/TPI with placebo in Asian metastatic colorectal cancer (mCRC) patients (pts) and demonstrated significant improvement in overall survival (OS) and progression‐free survival (PFS). Here we present the results of our country subgroup analysis from the TERRA study. Methods: The study enrolled pts who had received at least 2 prior standard regimens for mCRC including fluoropyrimidines, oxaliplatin and irinotecan. Eligible pts were randomized (2:1 ratio, minimization method) to receive FTD/TPI (35 mg/m2/dose, twice daily orally, 5 days on/2 days off for 2 weeks, followed by 14 days off per cycle) or placebo in each country. The efficacy and safety data of FTD/TPI versus placebo was evaluated for each country subgroup: China (CN), Republic of Korea (KR) and Thailand (TH). Results: There were 406 pts randomized: 305 CN (75.1%), 81 KR (20.0%) and20TH (4.9%). FTD/TPI demonstrated an improvement in OS and PFS versus placebo in all three countries (Table). Hazard ratios of OS in CN, KR and TH were 0.82, 0.77 and 0.54 respectively. The most common NCI‐CTCAE v4.0 grade >3 AEs in all countries were hematological AEs. More than 30% of pts had neutropenia of grade 3 or higher in the FTD/TPI group in each country; however, no febrile neutropenia was reported. The incidence of grade >3treatment emergent adverse events (TEAE) of nausea, vomiting and diarrhea in FTD/TPI group in each country were less than 2%. Table: 142O CN KR TH Overall FTD/Placebo FTD/Placebo FTD/Placebo FTD/Placebo TPITPITPITPI No.of pts 204 10155 2612 8271 135 OS HR 0.82 (0.62‐0.77(0.48‐0.54 (0.19‐0.79 (0.62‐(95% Cl) 1.08)1.26)1.53)0.99) PFS HR 0.41 (0.31‐0.56 (0.34‐0.54 (0.20‐0.43 (0.34‐(95% Cl) 0.54)0.93)1.42)0.54) Conclusions: FTD/TPI provided survival benefits in mCRC to patients in each of the countries in the study. Previously reported safety profiles were similar to the results from the TERRA study. FTD/TPI has the potential to be a new option for third‐line or later treatments for mCRC patients in Asia.