PMID- 34997449
OWN - NLM
STAT- MEDLINE
DCOM- 20220419
LR  - 20220716
IS  - 1436-3305 (Electronic)
IS  - 1436-3291 (Print)
IS  - 1436-3291 (Linking)
VI  - 25
IP  - 3
DP  - 2022 May
TI  - Efficacy and safety of trifluridine/tipiracil in older and younger patients with 
      metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a 
      randomized phase 3 study (TAGS).
PG  - 586-597
LID - 10.1007/s10120-021-01271-9 [doi]
AB  - BACKGROUND: Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs 
      placebo and manageable safety in previously treated patients with metastatic 
      gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, 
      placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined 
      efficacy/safety outcomes by age. METHODS: In TAGS, patients with mGC/GEJC and >/= 2 
      prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m(2) or placebo, 
      plus best supportive care. A preplanned subgroup analysis was performed to 
      evaluate efficacy and safety outcomes in patients aged < 65, >/= 65, 
      and >/= 75 years. RESULTS: Among 507 randomized patients (n = 337 FTD/TPI; n = 170 
      placebo), 55%, 45%, and 14% were aged < 65, >/= 65, and >/= 75 years, respectively. 
      Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 
      0.51-0.89), 0.73 (95% CI 0.52-1.02), and 0.67 (95% CI 0.33-1.37) in patients 
      aged < 65, >/= 65, and >/= 75 years, respectively. Regardless of age, patients 
      receiving FTD/TPI experienced improved progression-free survival and stayed 
      longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, 
      frequencies of any-cause grade >/= 3 adverse events (AEs) were similar across age 
      subgroups (80% each), although grade >/= 3 neutropenia was more frequent in older 
      patients [40% (>/= 65 and >/= 75 years); 29% (< 65 years)]; AE-related 
      discontinuation rates did not increase with age [14% (< 65 years), 12% 
      (>/= 65 years), and 12% (>/= 75 years)]. CONCLUSIONS: The results of this subgroup 
      analysis show the efficacy and tolerability of FTD/TPI treatment regardless of 
      age in patients with mGC/GEJC who had received 2 or more prior treatments.
CI  - (c) 2021. The Author(s).
FAU - Shitara, Kohei
AU  - Shitara K
AUID- ORCID: 0000-0001-5196-3630
AD  - Department of Gastrointestinal Oncology, National Cancer Center Hospital East, 
      Kashiwa-shi, Chiba, 277-8577, Japan. kshitara@east.ncc.go.jp.
FAU - Doi, Toshihiko
AU  - Doi T
AD  - Department of Gastrointestinal Oncology, National Cancer Center Hospital East, 
      Kashiwa-shi, Chiba, 277-8577, Japan.
FAU - Hosaka, Hisashi
AU  - Hosaka H
AD  - Department of Gastroenterology, Gunma Prefectural Cancer Center, Ota, Gunma, 
      Japan.
FAU - Thuss-Patience, Peter
AU  - Thuss-Patience P
AD  - Medizinische Klinik m.S. Hamatologie, Onkologie und Tumorimmunologie, 
      Charite-Universitatsmedizin Berlin, Berlin, Germany.
FAU - Santoro, Armando
AU  - Santoro A
AD  - Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 
      4, Pieve Emanuele, 20072, Milan, Italy.
AD  - IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Via Manzoni 56, 
      Rozzano, 20089, Milan, Italy.
FAU - Longo, Federico
AU  - Longo F
AD  - Medical Oncology, Hospital Universitario Ramon y Cajal, IRYCIS, CIBERONC, Madrid, 
      Spain.
FAU - Ozyilkan, Ozgur
AU  - Ozyilkan O
AD  - Medical Oncology, Baskent University Adana Practice and Research Centre Kisla, 
      Adana, Turkey.
FAU - Cicin, Irfan
AU  - Cicin I
AD  - Department of Internal Medicine, Division of Medical Oncology, School of 
      Medicine, Trakya University, Edirne, Turkey.
FAU - Park, David
AU  - Park D
AD  - Hematology and Oncology, St. Jude Crosson Cancer Institute/St. Joseph Heritage 
      Healthcare, Fullerton, CA, USA.
FAU - Zaanan, Aziz
AU  - Zaanan A
AD  - Department of Gastrointestinal Oncology, European Georges Pompidou Hospital, 
      AP-HP Centre, University of Paris, Paris, France.
FAU - Pericay, Carles
AU  - Pericay C
AD  - Medical Oncology, Corporacion Sanitaria Parc Tauli, Barcelona, Spain.
FAU - Ozguroglu, Mustafa
AU  - Ozguroglu M
AD  - Department of Internal Medicine, Division of Medical Oncology, Clinical Trial 
      Unit, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, 
      Turkey.
FAU - Alsina, Maria
AU  - Alsina M
AD  - Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), 
      Barcelona, Spain.
FAU - Makris, Lukas
AU  - Makris L
AD  - Stathmi, Inc., New Hope, PA, USA.
FAU - Benhadji, Karim A
AU  - Benhadji KA
AD  - Clinical Development, Taiho Oncology, Inc., Princeton, NJ, USA.
FAU - Ilson, David H
AU  - Ilson DH
AD  - Gastrointestinal Oncology Service in the Department of Medicine, Memorial Sloan 
      Kettering Cancer Center, New York, NY, USA.
LA  - eng
GR  - P30 CA008748/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20220108
PL  - Japan
TA  - Gastric Cancer
JT  - Gastric cancer : official journal of the International Gastric Cancer Association 
      and the Japanese Gastric Cancer Association
JID - 100886238
RN  - 0 (Drug Combinations)
RN  - 0 (Pyrrolidines)
RN  - 0 (trifluridine tipiracil drug combination)
RN  - NGO10K751P (tipiracil)
RN  - QR26YLT7LT (Thymine)
RN  - RMW9V5RW38 (Trifluridine)
SB  - IM
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Colorectal Neoplasms/pathology
MH  - Drug Combinations
MH  - *Esophageal Neoplasms/drug therapy
MH  - Esophagogastric Junction/pathology
MH  - *Frontotemporal Dementia/chemically induced/drug therapy
MH  - Humans
MH  - Pyrrolidines
MH  - *Stomach Neoplasms/pathology
MH  - Thymine
MH  - Trifluridine/adverse effects
PMC - PMC9013328
OTO - NOTNLM
OT  - Age groups
OT  - Aged
OT  - Gastrointestinal neoplasms
OT  - Randomized controlled trial
OT  - Stomach neoplasms
OT  - Trifluridine tipiracil
COIS- Kohei Shitara received honoraria from Novartis, AbbVie Inc, and Yakult; research 
      funding from Dainippon Sumitomo Pharma, Daiichi Sankyo, Taiho Pharmaceutical, 
      Chugai Pharma, Merck Pharmaceutical, Medi Science, and Eisai; and fees as an 
      advisor to Novartis, AbbVie Inc, Daiichi Sankyo, Taiho Pharmaceutical, Merck 
      Pharmaceutical, GlaxoSmithKline, Amgen, and Boehringer Ingelheim. Toshihiko Doi 
      received personal fees from Lilly, MSD, Daiichi Sankyo, Amgen, Sumitomo 
      Dainippon, Taiho, Novartis, Boehringer Ingelheim, Takeda, Chugai Pharma, 
      Bristol-Myers Squibb, AbbVie, Bayer, Rakuten Medical, Ono Pharmaceutical, 
      Astellas Pharma, and Oncolys BioPharma; and grants from Lilly, MSD, Daiichi 
      Sankyo, Sumitomo Dainippon, Taiho, Novartis, Merck Serono, Janssen, Boehringer 
      Ingelheim, Pfizer, Bristol-Myers Squibb, AbbVie, Quintiles, and Eisai. Hisashi 
      Hosaka received grants from Taiho Pharmaceutical Co., Ltd. Peter Thuss-Patience 
      served on advisory boards and received personal fees from Servier, Roche, BMS, 
      MSD, Lilly, Merck Serono, Pfizer, and AstraZeneca. Armando Santoro served on 
      advisory boards for BMS, Servier, Gilead, Pfizer, Eisai, Bayer, and MSD; as a 
      consultant for ArQule and Sanofi; and as a speaker for Takeda, BMS, Roche, 
      AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, ArQule, Eli Lilly, 
      Sandoz, Eisai, Novartis, Bayer, and MSD. Federico Longo received fees as an 
      advisor, non-financial support, and travel for meetings from Servier, Lilly, 
      Roche, BMS, MSD, Amgen, and Merck; and institutional grant funding from MSD. Aziz 
      Zaanan served on advisory boards and received personal fees from Amgen, Merck, 
      Roche, Sanofi, Servier, MSD, Pierre Fabre, Havas Life, Alira Health, and 
      Zymeworks. Maria Alsina received fees as an advisor to MSD, BMS, Servier, and 
      Lilly. Lukas Makris provided statistical design and analysis to Taiho Oncology, 
      Inc. (during and outside the conduct of the study); and has provided statistical 
      design and analysis services to other pharmaceutical companies and Independent 
      Data Monitoring Committees. Karim A Benhadji is an employee of Taiho Oncology, 
      Inc. and a former employee and stockholder of Eli Lilly. David H. Ilson served on 
      advisory boards and received personal fees from Taiho (during conduct of the 
      study), Roche, Merck, Bristol Myers Squibb, and Astellas. Ozgur Ozyilkan, Irfan 
      Cicin, David Park, Carles Pericay, and Mustafa Ozguroglu declare that they have 
      no conflict of interest.
EDAT- 2022/01/09 06:00
MHDA- 2022/04/20 06:00
PMCR- 2022/01/08
CRDT- 2022/01/08 06:11
PHST- 2021/07/02 00:00 [received]
PHST- 2021/11/26 00:00 [accepted]
PHST- 2022/01/09 06:00 [pubmed]
PHST- 2022/04/20 06:00 [medline]
PHST- 2022/01/08 06:11 [entrez]
PHST- 2022/01/08 00:00 [pmc-release]
AID - 10.1007/s10120-021-01271-9 [pii]
AID - 1271 [pii]
AID - 10.1007/s10120-021-01271-9 [doi]
PST - ppublish
SO  - Gastric Cancer. 2022 May;25(3):586-597. doi: 10.1007/s10120-021-01271-9. Epub 
      2022 Jan 8.