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Taiho Pharmaceutical Co., Ltd. announced today that the Japanese Ministry of Health, Labour and Welfare has approved an additional indication of postoperative adjuvant chemotherapy for hormone receptor-positive and HER2-negative breast cancer at high risk of recurrence for its oral anticancer agent TS-1 combination capsules T20/T25, TS-1 combination granules T20/T25, and TS-1 combination OD tablets T20/T25 (generic name: tegafur, gimeracil, oteracil potassium, hereafter “TS-1”).

This approval is based on the results of an investigator-initiated study, “Postoperative Therapy with TS-1 for oestrogen receptor-positive, HER2-negative breast cancer “(POTENT^* study). According to the results of the POTENT study, the combination of TS-1 with endocrine therapy showed a clinically significant extension of invasive disease-free survival (iDFS) among patients with oestrogen receptor-positive, HER2-negative breast cancer with an intermediate or higher risk of recurrence. The safety profile was similar to that of TS-1 reported in the past, and no new concerns were identified in the POTENT study.

^*POTENT : PostOperative Therapy with ENdocrine and TS-1

Taiho Pharmaceutical believes that TS-1 will make a positive contribution as a new treatment option for patients with breast cancer.

POTENT is an investigator-initiated study conducted since March 25, 2011, under the designation of advanced medical care (Specific Clinical Research jRCTs051180057, UMIN000003969). The principal investigator, Masakazu Toi, M.D., Ph.D., Professor of Breast Surgery at Kyoto University’s Graduate School of Medicine and Faculty of Medicine, had submitted a study application to the Japanese Ministry of Health, Labour and Welfare under the former Advanced Medical Care Program. On January 25, 2011, the Advanced Medical Care Assessment Council approved the study with the advanced medical care name, “Postoperative Therapy with TS-1 for oestrogen receptor-positive, HER2-negative breast cancer.”

The purpose of the study was to verify any increase in the effect on prevention of recurrence through a randomized comparative Phase III study in postoperative adjuvant therapy for oestrogen receptor-positive, HER2-negative breast cancer. The control group was treated with endocrine therapy (5 years), the standard treatment method, with the study group treated with endocrine therapy (5 years) in combination with TS-1 (1 year). The study endpoints included invasive disease-free survival, overall survival, safety, etc. The study enrolled 1,959 women from 139 breast cancer facilities across Japan during the registration period from February 2012 to February 2016.¹

Public Health Research Center, contracted to serve as the study management office, received funding from Taiho Pharmaceutical and this study was conducted with such funding. .

1 Toi M et al., Lancet Oncol 2021; 22: 74–84.

For more information of the POTENT study, please refer to

According to the Japan Breast Cancer Society’s Annual Report of the Japanese Breast Cancer Registry for 2017,² 94,612 women in Japan are affected by breast cancer annually. It is reported that 75.3% of these cases are oestrogen receptor-positive, HER2-negative breast cancer. In cases of early-stage breast cancer, perioperative chemotherapy and postoperative endocrine therapy are given as standard treatments in addition to surgery, considering the risk of recurrence.

2 Hayashi N et al., Breast Cancer 2020; 27:803–809.

A member of the fluoropyrimidine class of anticancer agents, TS-1 is a combination of three pharmacological compounds: tegafur, an antimetabolite agent that, after absorption by the gastrointestinal tract, is converted into the anticancer agent fluorouracil (5-FU); gimeracil (5-chloro-2, 4-dihydroxypyridine, or CDHP), which decreases the degradation of 5-FU in the body; and oteracil potassium (Oxo), which decreases 5-FU phosphorylation in the gastrointestinal tract. Developed as a gastric cancer treatment, TS-1 was first approved in Japan in 1999 and has become a standard of care for the treatment of gastric cancer. TS-1 has so far been approved in Japan for the treatment of gastric, colorectal, head and neck, non-small cell lung, inoperable or recurrent breast, pancreatic, and biliary tract cancers.

(Newly approved indication is underlined.)

Product name	TS-1 combination capsules T20/T25 TS-1 combination granules T20/T25 TS-1 combination OD tablets T20/T25
Indications	Gastric cancer, colorectal cancer, head and neck cancer, non-small cell lung cancer, inoperable or recurrent breast cancer, pancreatic cancer, biliary tract cancer, postoperative adjuvant chemotherapy for hormone receptor-positive and HER2-negative breast cancer at high risk of recurrence
Dosage and administration	<Gastric cancer, colorectal cancer, head and neck cancer, non-small cell lung cancer, inoperable or recurrent breast cancer, pancreatic cancer, biliary tract cancer> Usually, the standard doses below are defined as the initial dose (single dose) for adults according to body surface area. TS-1 is administered twice daily, after breakfast and after the evening meal, for 28 consecutive days, followed by a 14-day rest. This is regarded as one course of the regimen. The initial dose can be decreased or increased according to the patient's condition. The doses are staged thus: 40 mg, 50 mg, 60 mg, and 75 mg. If no drug-induced abnormalities in laboratory findings (hematological tests, liver and renal function tests) and no gastrointestinal symptoms occur, i.e., the drug is not problematic in terms of safety, and it is decided to increase the dose, the initial dose can be increased one stage, with an upper limit of 75 mg. It can also be decreased by one stage, and the lower limit is 40 mg. <Postoperative adjuvant chemotherapy for hormone receptor-positive and HER2-negative breast cancer at high risk of recurrence> Usually, the standard doses below are defined as the initial dose (single dose) for adults according to body surface area. TS-1 is administered twice daily in combination with endocrine therapy, after breakfast and after the evening meal, for 14 consecutive days, followed by a 7-day rest. This is regarded as one course of the regimen and continue up to 1 year. The initial dose can be decreased or increased according to the patient's condition. The dose should not be increased more than the patient’s initial dose.