Embryo-Fetal Toxicity: LONSURF can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with LONSURF.

USE IN SPECIFIC POPULATIONS

Lactation: It is not known whether LONSURF or its metabolites are present in human milk. There are no data to assess the effects of LONSURF or its metabolites on the breast-fed infant or the effects on milk production. Because of the potential for serious adverse reactions in breast-fed infants, advise women not to breastfeed during treatment with LONSURF and for 1 day following the final dose.

Male Contraception: Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with LONSURF and for at least 3 months after the final dose.

Geriatric Use: Patients 65 years of age or over who received LONSURF had a higher incidence of the following compared to patients younger than 65 years: Grade 3 or 4 neutropenia (48% vs. 30%), Grade 3 anemia (26% vs. 12%), and Grade 3 or 4 thrombocytopenia (9% vs. 2%).

Renal Impairment: In Study 1, patients with moderate renal impairment (CLcr=30 to 59 mL/min, n=47) had a higher incidence (difference of at least 5%) of greater than or equal to Grade 3 adverse events, serious adverse events, and dose delays and reductions compared to patients with normal renal function (CLcr greater than or equal to 90 mL/min, n=306) or patients with mild renal impairment (CLcr=60 to 89 mL/min, n=178).

Patients with moderate renal impairment may require dose modifications for increased toxicity. No patients with severe renal impairment were enrolled in Study 1.

ADVERSE REACTIONS

Most Common Adverse Drug Reactions in Patients Treated With LONSURF (greater than or equal to 5%): The most common adverse drug reactions in LONSURF-treated patients vs. placebo-treated patients with refractory mCRC, respectively, were asthenia/fatigue (52% vs. 35%), nausea (48% vs. 24%), decreased appetite (39% vs. 29%), diarrhea (32% vs. 12%), vomiting (28% vs. 14%), abdominal pain (21% vs. 18%), pyrexia (19% vs. 14%), stomatitis (8% vs. 6%), dysgeusia (7% vs. 2%), and alopecia (7% vs. 1%).

Additional Important Adverse Drug Reactions: The following occurred more frequently in LONSURF-treated patients compared to placebo: infections (27% vs. 15%) and pulmonary emboli (2% vs. 0%).

The most commonly reported infections which occurred more frequently in LONSURF-treated patients were nasopharyngitis (4% vs. 2%) and urinary tract infections (4% vs. 2%).

Interstitial lung disease (0.2%), including fatalities, has been reported in clinical studies and clinical practice settings in Asia.

Laboratory Test Abnormalities in Patients Treated With LONSURF: Laboratory test abnormalities in LONSURF-treated patients vs. placebo-treated patients with refractory mCRC, respectively, were anemia (77% vs. 33%), neutropenia (67% vs. 1%), and thrombocytopenia (42% vs. 8%).

Please see Full Prescribing Information.

www.taihooncology.com/us/prescribing-information.pdf

About Taiho Pharmaceutical Co., Ltd. (Japan)

Taiho Pharmaceutical, a subsidiary of Otsuka Holdings Co., Ltd., is an R&D-driven specialty pharma focusing on the three fields of oncology, allergies and immunology, and urology. Its corporate philosophy takes the form of a pledge: "We strive to improve human health and contribute to a society enriched by smiles." In the field of oncology in particular, Taiho Pharmaceutical is known as a leading company in Japan for developing innovative medicines for the treatment of cancer. In areas other than oncology, as well, the company creates quality products that effectively treat medical conditions and can help improve people's quality of life. Always putting customers first, Taiho Pharmaceutical aims to also offer over-the-counter medicinal products that support people's efforts to lead fulfilling and rewarding lives.

For more information about Taiho Pharmaceutical, please visit: http://www.taiho.co.jp/english/.

About Taiho Oncology, Inc. (U.S.)

Taiho Oncology, Inc., a subsidiary of Taiho Pharmaceutical Co., Ltd. and Otsuka Holdings Co., Ltd., has established a world-class clinical development organization that works urgently to develop innovative cancer treatments and has built a commercial business in the U.S. Taiho Oncology has an oral oncology pipeline consisting of both novel antimetabolic agents and selectively targeted agents. Advanced technology, dedicated researchers, and state-of-the-art facilities are helping us to define the way the world treats cancer. It's our work; it's our passion; it's our legacy.

For more information about Taiho Oncology, please visit: www.taihooncology.com

(*1) http://globocan.iarc.fr/old/summary_table_pop-html.asp?selection=7967&title=Asia&sex=0&type=1&window=1&sort=2&submit=%A0Execute%A0   (analysed March 16th, 2016)

(*2) FDA News Release. FDA approves new oral medication to treat patients with advanced colorectal cancer. 22 September 2015. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm463650.htm Accessed March 2016

(*3) Taiho Pharmaceutical News Release. Taiho's Lonsurf (R) (trifluridine and tipiracil hydrochloride) Tablets Approved in Japan for Treatment in Advanced Metastatic Colorectal Cancer. Available at: http://www.taiho.co.jp/english/news/20140324.html Accessed March 2016

(*4) Committee for Medicinal Products for Human Use (CHMP) Summary of opinion. http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_-_Initial_authorisation/human/003897/WC500202369.pdf

(*5) LONSURF Summary of Product Characteristics