Last reviewed: August 2019
Last updated: April  2019
18 Apr 2019

US FDA approves trifluridine/tipiracil for metastatic gastric cancer after trial shows it improves survival

A trifluridine/tipiracil combination tablet has been approved by the US Food and Drug Administration for adults with nonresectable metastatic gastric adenocarcinoma who have received at least two previous chemotherapy regimens and experienced radiologic disease progression.

The approval is based on the results of the double-blind, placebo-controlled TAGS trial, which reported: [33]

  • Significantly improved median overall survival among patients with non-resectable metastatic gastric adenocarcinoma who were randomised to trifluridine/tipiracil (5.7 vs. 3.6 months in the placebo group; hazard ratio: 0.69, 95% CI 0.56 to 0.85). Trifluridine/tipiracil was also associated with improved progression-free survival.

  • Of the 507 patients enrolled in the trial, more than 60% had received at least three previous chemotherapy regimens (211 out of 337 patients in the trifluridine/tipiracil group and 106 out of 170 in the placebo group). The most frequently reported grade 3 (severe but not life-threatening) or worse adverse events in the trifluridine/tipiracil group were neutropenia (114 [34%]), anaemia (64 [19%]), and leukopenia (31 [9%]).

The combination tablet of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, is already approved for the treatment of advanced refractory colorectal cancer.

Pre-registration for this new advanced gastric cancer indication was filed in the EU in October 2018 and is awaiting approval.

See Management: approach See Management: treatment algorithm

Original source of update



History and exam

Key diagnostic factors

  • presence of risk factors
  • abdominal pain
  • weight loss
  • lymphadenopathy

Other diagnostic factors

  • age 50 to 70 years
  • male sex
  • smoking
  • family history
  • nausea
  • dysphagia
  • lower gastrointestinal bleeding

Risk factors

  • pernicious anaemia
  • Helicobacter pylori
  • N-nitroso compounds
  • diet low in fruits and vegetables
  • high-salt diet
  • smoking
  • family history

Diagnostic investigations

1st investigations to order

  • upper gastrointestinal endoscopy with biopsy
Full details

Investigations to consider

  • endoscopic ultrasound (EUS)
  • computed tomography of abdomen/pelvis
  • chest x-ray
  • computed tomography of chest
  • laparoscopy
  • positron emission tomography/computed tomography scan
Full details

Treatment algorithm


Authors VIEW ALL

Associate Professor

Department of GI Medical Oncology

University of Texas

MD Anderson Cancer Center




MBM declares that she has no competing interests.

Dr Mariela Blum Murphy would like to gratefully acknowledge Dr Valerie Reed and Dr Prajnan Das, previous contributors to this topic.

Peer reviewers VIEW ALL


Gastrointestinal Radiation Oncology

Massachusetts General Hospital Cancer Center




TH declares that he has no competing interests.

Head of Department

Department of Gastroenterology

Sana Klinikum




AL declares that he has no competing interests.

Use of this content is subject to our disclaimer