FDA Approves Combo Drug for Metastatic Gastric Cancer

Nick Mulcahy


February 25, 2019

Patients with metastatic gastric adenocarcinoma, including that of the gastroesophageal junction, who don't respond to other therapies now have another option.

The US Food and Drug Administration (FDA) has approved the combination product trifluridine/tipiracil (Lonsurf, Taiho Oncology) for pretreated metastatic gastric cancer, addressing an unmet need in oncology.

The agent is a two-drugs-in-one-pill combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor.

The therapy is already FDA-approved for the treatment of advanced refractory colorectal cancer.

Approval of the new indication is based on results from the phase 3 randomized trial known as TAGS, results of which were presented in June 2018 at the World Congress on Gastrointestinal Cancer, as reported by Medscape Medical News.  

At the time, David Cunningham, MD, consultant medical oncologist, Royal Marsden NHS Foundation Trust, Surrey, United Kingdom, said the new therapy addresses an unmet need.

"We have nothing else we can offer those patients, and this study shows that we can extend life expectancy and improve disease control rates up to a very significant level," explained Cunningham, who was not involved in the study.

The TAGS study results have since been published in The Lancet Oncology.

The trial was conducted in 507 patients with nonresectable metastatic gastric adenocarcinoma who were assigned (2:1) to the trifluridine/tipiracil group (n = 337) or placebo group (n = 170).

Patients had received at least two previous chemotherapy regimens and experienced radiological disease progression.

The primary endpoint of median overall survival was 5.7 months in the trifluridine/tipiracil group and 3.6 months in the placebo group (hazard ratio [HR], 0.69; 95% CI, 0.56 - 0.85; one-sided P = .00029, two-sided P = .00058).

Grade 3 or worse adverse events occurred in 80% of the trifluridine/tipiracil group and 58% of the placebo group.

The most frequent grade 3 or worse adverse events were neutropenia (34%) and anemia (19%) in the trifluridine/tipiracil group and abdominal pain (9%) and general deterioration of physical health (9%) in the placebo group.

Serious adverse events occurred in 43% of patients in the trifluridine/tipiracil group and 42% in the placebo group.

One treatment-related death was reported in each group (because of cardiopulmonary arrest in the trifluridine/tipiracil group and toxic hepatitis in the placebo group).

The recommended dose for the new drug is 35 mg/m2/dose orally twice daily on days 1 through 5 and days 8 through 12 of each 28-day cycle.

In TAGS, the median age was 64 years in the trifluridine/tipiracil group and 62.5 years in the placebo group; 75% and 69% of patients, respectively, were men. In both groups, the primary tumor site was gastric in 71% of cases, while 54% and 58% of patients in both groups, respectively, had three or more metastatic sites.

More than 60% of patients in both groups had received at least three prior treatment regimens. The most commonly used agents included fluoropyrimidine, platinum, taxane, and irinotecan.

TAGS was conducted in 17 countries and regions including Belarus, the European Union, Israel, Japan, North America, Russia, and Turkey.

TAGS was funded by Taiho Oncology.

Lancet Oncol. 2018;19:1437-1448. Full text

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