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: 
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
Presenting symptoms can include weight loss and abdominal pain, although patients with proximal or gastro-oesophageal junction tumours may present with dysphagia.
Upper gastrointestinal endoscopy with biopsy demonstrating carcinoma is required to confirm the diagnosis. Staging based on imaging is required.
Early-stage disease is treated with surgery alone.
Locally advanced disease is treated with multimodality approach that includes surgery followed by postoperative chemoradiation, or chemotherapy before and after surgery.
Metastatic disease is treated with chemotherapy, immunotherapy, or chemoradiation and supportive care measures.
Common complications are gastric bleeding and gastric outlet obstruction.
Stomach cancer is a neoplasm that can develop in any portion of the stomach and may spread to the lymph nodes and other organs. Most tumours are adenocarcinomas. Other histological types include lymphoma, leiomyosarcoma, neuroendocrine tumours, and squamous cell carcinomas, but these are uncommon and will not be discussed here.
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.
Gastrointestinal Radiation Oncology
Massachusetts General Hospital Cancer Center
TH declares that he has no competing interests.
Head of Department
Department of Gastroenterology
AL declares that he has no competing interests.
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