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Taiho Pharmaceutical Co., Ltd. (HQ: Tokyo, President: Masayuki Kobayashi) announced today that it had presented the results of the following Phase III trials conducted in Japan at the 49th Annual Meeting of the American Society of Clinical Oncology® (ASCO®) held in Chicago, Illinois from May 31 to June 4, 2013: An ACTS-CC trial (subjects: resected stage III colon cancer patients), a SOFT trial (subjects: patients with metastatic colorectal cancer), and an ACTS-HNC trial (subjects: patients with squamous cell carcinoma of the head and neck after curative treatment).

The efficacy of TS-1 was investigated for the first time worldwide in resected colon cancer patients in the ACTS-CC trial, and in head and neck cancer patients after curative treatment in the ACTS-HNC trial. The SOFT trial was the first Phase III trial investigating the efficacy of TS-1 + Oxaliplatin and combined use of Bevacizumab as first-line chemotherapy in patients with metastatic colorectal cancer. The results of these trials represent a major contribution to medical professionals engaged in cancer treatment as well as patients undergoing cancer treatment.

Taiho Pharmaceutical remains dedicated to continuing its efforts to develop new cancer treatments.

ACTS-CC Trial
Summary
Taiho Pharmaceutical subcontracted Translational Research Informatics Center (TRI; Foundation for Biomedical Research and Innovation) to carry out a Phase III trial comparing TS-1 with a standard treatment UFT/LV in patients with resected stage III colon cancer. The trial demonstrated the non-inferiority of TS-1 in disease- free survival (DFS).

Results
The trial showed that 3-year DFS was 75.5% in the TS-1 group and 72.5% in the UFT/LV group, demonstrating the non-inferiority of TS-1 in DFS (HR = 0.85; 95% CI: 0.70-1.03, non-inferiority test p<0.0001). Adverse events of grade 3 or higher in the TS-1 and UFT/LV groups respectively were diarrhea (4.4%:5.5%), loss of appetite (4.9%:3.5%), elevated total bilirubin value (1.2%:1.5%), elevated AST (0.8%:2.1%), and elevated ALT (1.1%:3.3%).

SOFT Trial
Summary
In this Phase III trial conducted by Taiho Pharmaceutical, TS-1/Oxaliplatin (SOX) + Bevacizumab (Bev) was compared to a standard treatment 5-FU/I-LV/Oxaliplatin (FOLFOX) + Bev in patients with metastatic colorectal cancer. The trial demonstrated the non-inferiority of SOX + Bev in progression- free survival (PFS).

Results
The PFS median value for SOX + Bev was 11.7 months (95% CI: 10.7-12.9) compared to 11.5 months for FOLFOX + Bev (95% CI: 10.7-13.2), which demonstrated the non-inferiority of SOX + Bev in comparison to FOLFOX + Bev (HR = 1.043; 95% CI: 0.860-1.266, non-inferiority test p=0.0139). Adverse events of grade 3 or higher in the SOX + Bev and FOLFOX + Bev groups respectively were: leukopenia (2.4%:8.4%), neutropenia (8.8%:33.7%), loss of appetite (5.2%:1.2%), and diarrhea (9.2%:2.8%).

ACTS-HNC Trial
Summary
Taiho Pharmaceutical subcontracted Translational Research Informatics Center (TRI; Foundation for Biomedical Research and Innovation) to carry out a Phase III trial comparing TS-1 with UFT in patients who underwent curative treatment for squamous cell carcinoma of the head and neck.

Results
The trial showed that 3-year DFS was 60.0% in the UFT group and 64.1% in the TS-1 group, which did not demonstrate the superiority of TS-1 in DFS (HR = 0.87; 95% CI: 0.66-1.16, p=0.34). However, the 3-year survival rate in the UFT group was 75.8% compared to 82.9% in the TS-1 group, which indicated a statistically significant advantage for the TS-1 group (HR = 0.64; 95% CI: 0.44-0.94, p=0.02). Adverse events of grade 3 or higher in the TS-1 group included the following (Note: figures in parentheses indicate the incidence rate of grade 3 and 4 adverse events in the TS-1 group): oral mucositis/stomatitis (2.4%), leukopenia (5.2%), neutropenia (3.6%), and thrombocytepenia (2.0%).

About TS-1
A member of the fluoropyrimidine class of chemotherapeutic agents, TS-1 is a combination of three pharmacological compounds: tegafur, an antimetabolite agent that, after absorption, is converted into the anti-cancer agent fluorouracil (5-FU); gimeracil (5-chloro-2, 4-dihydroxypyridine, or CDHP), which decreases the degradation of 5-FU in the liver; and oteracil (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 was subsequently approved in Japan for six additional indications: for the treatment of colorectal, head and neck, non-small cell lung, and inoperable or recurrent breast, pancreatic, and biliary tract cancers. TS-1 is also approved for patients with gastric cancer in 7 countries* in Asia, and in 15 European countries.*

• As of May 15, 2013.