465PD - TERRA: a randomized, double-blind, placebo-controlled phase 3 study of TAS-102 in Asian patients with metastatic colorectal cancer

Date 10 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, colorectal
Topics Cytotoxic agents
Colon and Rectal Cancer
Therapy
Biological therapy
Presenter Tae Won Kim
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors T.W. Kim1, L. Shen2, J.M. Xu3, V. Sriuranpong4, H. Pan5, R. Xu6, S. Han7, T. Liu8, Y.S. Park9, C. Shir10, Y. Bai11, F. Bi12, J.B. Ahn13, S. Qin14, Q. Li15, C. Wu16, F. Zhou17, D. Ma18, V. Srimuninnimit19, J. Li20
  • 1Department Of Oncology, Asan Medical Center, 138-736 - Seoul/KR
  • 2Gastrointestinal Oncology, Peking University Cancer Hospital, Beijing/CN
  • 3Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, 100071 - Beijing/CN
  • 4Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, 10330 - Bangkok/TH
  • 5Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016 - Hangzhou/CN
  • 6Medical Oncology, Cancer Centre Sun Yat-Sen University, 510060 - Guangzhou/CN
  • 7Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 8Medical Oncology, Zhongshan Hospital Fudan University, Shanghai/CN
  • 9Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, Seoul/KR
  • 10Oncology, Fujian Medical University Union Hospital, Fuzhou/CN
  • 11Digestive Oncology, Harbin Medical University Cancer Hospital, Harbin/CN
  • 12Abdomen Oncology, West China Hospital, Sichuan University, Chengdu/CN
  • 13Internal Medicine, Yonsei University College of Medicine, Seoul/KR
  • 14Medical Oncology, No. 81 Hospital of PLA, 210002 - Nanjing/CN
  • 15Oncology, Shanghai First People's Hospital Affiliated Shanghai Jiaotong University, Shanghai/CN
  • 16Oncology, The First People's Hospital of Changzhou, Changzhou/CN
  • 17Medical And Radiation Oncology, Zhongnan Hospital of Wuhan University, Wuhan/CN
  • 18Medical Oncology, Guangdong General Hospital, Guangzhou/CN
  • 19Medical Oncology Division, Siriraj Hospital, Mahidol University, 10700 - Bangkok/TH
  • 20Medical Oncology, Tongji University Affiliate Tianyou Hospital, Shanghai/CN

Abstract

Background

The RECOURSE study demonstrated that trifluridine/tipiracil hydrochloride (TAS-102) significantly improved overall survival (OS) and progression-free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC) who had failed standard therapies. In the TERRA study, the efficacy and safety of TAS-102 were evaluated in similar Asian population with mCRC who had failed conventional cytotoxic therapies.

Methods

This was a multicenter, randomized, double-blind, placebo-controlled phase 3 study. Pts must have had received at least 2 prior standard regimens for mCRC, including fluoropyrimidines, oxaliplatin, and irinotecan. Prior anti-VEGF or anti-EGFR targeted therapy was not mandatory therapy. Between 16 Oct, 2013 and 15 Jun, 2015, 516 pts were screened and 406 pts were enrolled. Pts were stratified by KRAS status and geographic region and were randomized in a 2:1 ratio to receive TAS-102 (35 mg/m2 BID on days 1-5 and 8-12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary endpoint was OS. Key secondary endpoints included PFS and safety.

Results

In the primary analysis, TAS-102 demonstrated an improvement in OS versus placebo, hazard ratio ([HR] 0.79; 95% confidence interval [CI] 0.62-0.99; P = 0.035) (the median OS were 7.8 versus 7.1 months, respectively). Improvement in PFS was also observed (HR: 0.43; 95% CI 0.34-0.54, P 

Conclusions

The TERRA study demonstrated an improvement in OS and PFS in Asian pts with mCRC who had failed conventional cytotoxic therapies. The safety profile of TAS-102 was similar to that in previous studies. A data according to the pre and post-study treatments, especially targeted therapies, will be presented.

Clinical trial identification

NCT01955837

Legal entity responsible for the study

Taiho Pharmaceutical Co., Ltd.

Funding

Taiho Pharmaceutical Co., Ltd.

Disclosure

T.W. Kim: Employment, leadership, Tock, Speaker's bureau, patients, expert testimony Travel expense: No Research fund: Roche, Merck Serono Consulting or advisory role: Bayer, Lilly All other authors have declared no conflicts of interest.