555P - Integrated safety summary (ISS) for trifluridine/tipiracil (TAS-102)

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Anticancer Agents
Colon and Rectal Cancer
Biological Therapy
Presenter Alfredo Falcone
Citation Annals of Oncology (2016) 27 (6): 149-206. 10.1093/annonc/mdw370
Authors A. Falcone1, A. Ohtsu2, E. Van Cutsem3, R. Mayer4, M. Buscaglia5, J.C. Bendell6, S. Kopetz7, M. Wahba8, P. Bebeau9, T. Yoshino10
  • 1Medical Oncology, Azienda Ospedaliero Universitaria Pisana, 56126 - Pisa/IT
  • 2Clinical Development, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 3Medicine (digestive Oncology), University Hospitals Leuven - Campus Gasthuisberg, 3000 - Leuven/BE
  • 4Gastrointestinal Cancer, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 5Medical Oncology, IRCCS AOU San Martino IST, 16132 - Genova/IT
  • 6Gi Oncology Research, Drug Development, Sarah Cannon Research Institute, Tennessee Oncology, 37203 - Nashville/US
  • 7Department Of Gastrointestinal (gi) Medical Oncology, Division Of Cancer Medicine, MD Anderson Cancer Center, Houston/US
  • 8Medical Affairs, Medical Pharmacovigilance, Taiho Oncology, Inc., 08540 - Princeton/US
  • 9Pharmacovigilance, Taiho Oncology, Inc., 08540 - Princeton/US
  • 10Medical Oncology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP



Efficacy and safety of trifluridine/tipiracil (FTD/TPI; TAS-102) in patients (pts) with metastatic colorectal cancer (mCRC) refractory/intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial; enrollment criteria included ≥2 prior lines of standard chemotherapy. RECOURSE showed significant improvement in overall survival (OS; hazard ratio [HR] = 0.68) and progression-free survival (PFS; HR = 0.48) with FTD/TPI vs placebo (pbo); both P 


The main safety analysis (Safety Data Group 2) was based on integrated safety (IS) data from RECOURSE and 1 other randomized, pbo-controlled study (J003) of mCRC pts treated with FTD/TPI at the recommended starting dose (RSD) of 35 mg/m2 BID for 5 d/wk with 2 d rest for 2 wks followed by a 14-d rest (1 cycle). IS data from a larger group included those 2 studies and 6 others of FTD/TPI in CRC pts treated with the same RSD (Group 1). Nonintegrated data on serious adverse events (SAEs) from all FTD/TPI clinical experience as of data cutoff date were also summarized.


FTD/TPI was generally well tolerated in both groups. There was a higher incidence of myelosuppressive AEs, including Grade 3 anemia and neutropenia, in FTD/TPI vs pbo in Group 2 (Table). All grades gastrointestinal (GI) AEs were more frequent in FTD/TPI (77.7%) vs pbo (60.6%), but overall incidence of Grade ≥3 GI AEs was similar in both (12.1% FTD/TPI, Group 1; 12.8% FTD/TPI vs 11.5% pbo, Group 2). Febrile neutropenia (Grade ≥3) was reported in 25 (3.9%) FTD/TPI vs 0 pbo pts, Group 2. For pts receiving FTD/TPI past data cutoff (n = 76), 12 pts had 15 SAEs, none fatal or life threatening; 2 were associated with FTD/TPI: Grade 3 febrile neutropenia and abdominal pain.


FTD/TPI was generally well tolerated; main toxicities were hematologic and GI, but resulted in a low rate of dose reduction, discontinuation, or incidence of severe events. This analysis confirms the safety profile observed in RECOURSE.

Safety Data Group 1a Safety Data Group 2b
FTD/TPI (n = 761) FTD/TPI (n = 646) Placebo (n = 322)
Overview of Grade ≥3 Adverse Events (AEs), n (%)
Any AE 521 (68.5) 448 (69.3) 146 (45.3)
AEs resulting in study discontinuation 51 (6.7) 47 (7.3) 31 (9.6)
AEs leading to study treatment interruption/delay or dose reduction 304 (39.9) 260 (40.2) 26 (8.1)
Serious AEs 177 (23.3) 158 (24.5) 85 (26.4)
Fatal AEs 20 (2.6) 18 (2.8) 30 (9.3)
Grade ≥3 AEs Reported by ≥5% of Patients in Any Treatment Group, n (%)
Anemia 106 (13.9) 88 (13.6) 7 (2.2)
Neutropenia 146 (19.2) 107 (16.6) 0

aSafety Data Group 1 included patients in Safety Data Group 2 plus patients in phase 1 studies TAS-102-101 and -102 (pharmacokinetics [PK] and initial tolerability); TAS-102-103 (cardiac safety); TAS-102-104 (bioavailability); J001 (PK/initial tolerability); and J004 (extrinsic factor PK). bSafety Data Group 2 included patients in studies J003 (phase 2) and RECOURSE (phase 3), both controlled efficacy and safety studies.

Clinical trial identification

Legal entity responsible for the study

Taiho Pharmaceutical Co., Ltd.


Taiho Pharmaceutical Co., Ltd.


A. Falcone: Honoraria, consulting/advisory role, participation in a speakers' bureau: Amgen, Bayer, Merck Serono, Roche, Sanofi, Lilly. A. Ohtsu: Employment with Celgene. Honoraria from Taiho, Eisai, Daiichi-Sankyo, Merck Serono, Chugai. R. Mayer: Compensation for consulting/advisory role from AstraZeneca, Amgen, Mikana Therapeutics. M. Wahba: Employment with Taiho Oncology, Inc. P. Bebeau: Employment with Taiho Oncology, Inc. T. Yoshino: Research funding from Sumitomo Dainippon Pharma Co., Ltd. All other authors have declared no conflicts of interest.