News Releases

Taiho Pharmaceutical Co., Ltd. today announced that the United States Food and Drug Administration (FDA) has approved LONSURF^® (trifluridine/tipiracil, TAS-102) as a treatment for adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy. LONSURF was granted priority review status in October 2018 by the FDA, allowing for a six-month FDA review period, rather than the standard ten-month review period.

LONSURF has been available worldwide including the United States, Europe, and Japan, as a treatment for metastatic colorectal cancer (mCRC). In the Unites States, this approval expands the current indication for LONSURF, the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy and, if RAS wild-type, an anti-EGFR therapy. Applications for an additional indication for advanced gastric cancer were also submitted and are currently under review in European Union and in Japan.

The approval is based on data from a global, randomized Phase III TAGS trial evaluating trifluridine/tipiracil plus best supportive care (BSC) versus placebo plus BSC in patients with previously treated advanced gastric or GEJ adenocarcinoma following progression or intolerance to previous lines of standard therapy. The trial met its primary endpoint demonstrating prolonged overall survival (OS) with trifluridine/tipiracil versus placebo, and a safety profile consistent with prior experience with this drug. Full results from the TAGS trial were presented at the ESMO 2018 Congress with a simultaneous publication in The Lancet Oncology.¹

Taiho remains committed to making further contributions to patients and to medical practitioners engaged in the treatment of cancer.

TAGS (TAS-102 Gastric Study) is a Taiho-sponsored, global, randomized, double-blind Phase III study evaluating trifluridine/tipiracil (TAS-102) plus BSC versus placebo plus BSC in patients with metastatic gastric or GEJ cancer, refractory to standard treatments. The primary endpoint in the TAGS trial was OS, and the main secondary endpoint measures included progression-free survival (PFS), safety and tolerability, as well as quality of life.

The TAGS trial aimed to enroll 500 adults 18 years and older, with metastatic gastric or GEJ cancer who had previously received at least two prior regimens for advanced disease. The trial enrolled 507 subjects and was conducted in 17 countries and 110 sites around the world.

For more information on the TAGS trial, please visit
www.ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02500043).
The ClinicalTrials.gov Identifier is NCT02500043.

Gastric cancer is the fifth most common cancer worldwide and the third most common cause of cancer-related death (after lung and liver cancer), with an estimated 723,000 deaths annually.²　

In the United States (U.S.), in 2018, there were an estimated 26,240 new cases and 10,800 deaths.³ Approximately 35 percent of U.S. patients with gastric cancer are diagnosed at the distant or metastasized stage.³ Metastatic gastric cancer is associated with a five-year survival rate of about 5 percent.³

Standard chemotherapy regimens in U.S. for advanced gastric cancer include fluoropyrimidines, platinum derivatives, and taxanes (with ramucirumab), or irinotecan. After failure of first- and second-line therapies, subsequent treatment options are limited.

LONSURF (trifluridine/tipiracil) is an oral anticancer drug, which utilizes the combination of trifluridine (FTD) and tipiracil (TPI), whose dual mechanism of action is designed to maintain clinical activity and differs from conventional fluoropyrimidines. FTD is an antineoplastic nucleoside analogue, which is incorporated directly into the DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.

In Japan, Taiho Pharmaceutical has been marketing LONSURF for the treatment of unresectable advanced or recurrent colorectal cancer since 2014. Taiho Oncology, Inc., a U.S. subsidiary of Taiho Pharmaceutical, has been marketing LONSURF in the United States for mCRC refractory to prior therapy, since receiving FDA approval in 2015. Taiho Pharmaceutical and Servier* are in an exclusive license agreement for the co-development and commercialization of LONSURF in Europe and other countries outside of the United States, Canada, Mexico, and Asia. In parts of Asia outside of Japan, Taiho Pharmaceutical’s business partner TTY Biopharm launched LONSURF in Taiwan in 2018, and Jeil Pharmaceutical is preparing to bring the drug to market in South Korea.

As of February 2019, LONSURF has been approved as a treatment option for advanced mCRC in 66 countries and regions worldwide

*Servier is an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes).

¹ Shitara, K., Doi, T., Dvorkin, M., et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet Oncology. 2018;19(11): 1437-1438. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30739-3/fulltext. Accessed February 2019.

² Ferlay J, Soerjomataram I, Dikshit R, et al. Int J Cancer. 2015;136:E359-86.

³ National Cancer Institute Surveillance Epidemiology and End Results Program. Cancer Stat Facts: Stomach Cancer. https://seer.cancer.gov/statfacts/html/stomach.html. Accessed February 2019.