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Trifluridine/Tipiracil and Ramucirumab Demonstrate Antitumor Activity in Previously Treated Unresectable Advanced Gastric or Gastroesophageal Cancer

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The third leading cause of cancer-related deaths globally is gastric cancer.1 Treatment of advanced metastatic gastric cancer is palliative, with the dual goals of improving quality of life and prolonging patient survival with palliative treatment and supportive care.1 Chemotherapy with fluoropyrimidine or platinum-based agents and irinotecan or taxane-based agents are common treatment regimens.1 In addition, antivascular endothelial growth factor monoclonal antibodies such as ramucirumab are also used as later-line therapies.1 Drug resistance is also common during treatment, necessitating the need for further therapy development.1

Trifluridine and tipiracil have been used to treat colorectal cancer as a fixed-dose combination tablet and has gained approval as a second-line or later therapy in patients with metastatic gastric cancer in the United States.1 In Japan, Kawazoe and colleagues conducted a phase 2 clinical trial in 64 patients with previously treated unresectable advanced gastric cancer or gastroesophageal junction cancer to investigate the use of trifluridine/tipiracil and ramucirumab in this patient population. The study’s primary end point was disease control rate. Safety was also evaluated during the study.

There were 33 patients in cohort A who had 1 previous line of chemotherapy, but no treatment with ramucirumab. In cohort B, 31 patients were enrolled who had 2 to 4 lines of chemotherapy in addition to treatment with ramucirumab. A dose of 35 mg/m2 of oral trifluridine/tipiracil was given twice a day, on days 1 to 5, and then again on days 8 to 12 of the 28-day treatment cycle. On days 1 and 15, 8 mg/kg of ramucirumab was given intravenously.

The disease control rate was 85% in cohort A and 77% in cohort B. Evaluation of treatment-related adverse events grade ≥3 found 82% of cohort A patients and 74% of cohort B patients experienced a decrease in neutrophil count, 24% of cohort A patients and 23% of cohort B patients had a decrease in white blood cell counts, and 24% of patients in cohort A and 13% of patients in cohort B had a decrease in platelets. In addition, 3 patients in cohort A had serious treatment-related adverse events. These included large intestine perforation, decreased neutrophil count, fatigue, anemia, decreased platelet count, and febrile neutropenia. There were no treatment-related deaths reported during the study period in either cohort.

The combination of trifluridine/tipiracil and ramucirumab had promising antitumor activity and a tolerable safety profile in this patient population, even in patients who had received previous treatment with ramucirumab.


Kawazoe A, Ando T, Hosaka H, et al. Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial. Lancet Gastroenterol Hepatol. 2021;6:209-217.


  1. Kang C, Dhillon S, Deeks ED. Trifluridine/tipiracil: a review in metastatic gastric cancer [published correction appears in Drugs. September 18, 2019]. Drugs. 2019;79:1583-1590.

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