TOKYO, Japan I April 1, 2016 I Taiho Pharmaceutical Co., Ltd. of Tokyo announced on April 1 results from its Phase III TERRA study on its oral combination anticancer drug TAS-102 (product name in Japan and the U.S. LONSURF (R), nonproprietary names: trifluridine (FTD) and tipiracil (TPI)) in Asian (China, South Korea and Thailand) patients with refractory metastatic colorectal cancer (mCRC). The TERRA study met its primary endpoint of demonstrating improvement in overall survival (OS) in patients with refractory mCRC whose disease had progressed after approved standard therapies. In this study, TAS-102 appeared to be generally well tolerated and its toxicities were consistent with what was previously reported.
More detailed results from this study will be presented at a future international academic conference.
The Taiho team is preparing for the NDAs of TAS-102 in Asian countries.
About TERRA study
The TERRA study is a randomized, double-blind, placebo-controlled Phase III comparison study evaluating the efficacy and safety of orally administered TAS-102 in patients with refractory mCRC. The study enrolled 406 patients who received at least two prior regimens of standard chemotherapies for mCRC and were refractory to, or failed, those chemotherapies. The study was conducted in China, South Korea, and Thailand. Patients were randomly assigned to receive either TAS-102 or placebo in order to investigate the efficacy of TAS-102. The primary objective of the TERRA study was improvement in overall survival (OS) versus placebo. The principal researchers are Prof. Jin Li of Shanghai Tianyou Hospital and Fudan University Shanghai Cancer Center (China), Prof. Tae Won Kim of Asan Medical Center (Korea), Prof. Virote Sriuranpong of Chulalongkorn University & the King Chulalongkorn Memorial Hospital (Thailand).
About Metastatic Colorectal Cancer in Asia
In Asia, the incidence of colorectal cancer is increasing and colorectal cancer is the fourth most common cancer cause of death after lung cancer, hepatic cancer and gastric cancer. In 2012, it is reported that 331,600 people in Asia died from colorectal cancer. (*1)
About LONSURF
LONSURF is currently available in Japan for the treatment of unresectable advanced or recurrent CRC and in the United States for 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. (*2, *3) LONSURF is marketed by Taiho Pharmaceutical in Japan and by Taiho Oncology, Inc., a subsidiary of Taiho Pharmaceutical, in the U.S. In June 2015, Taiho Pharmaceutical entered into an exclusive license agreement with Servier for the co-development and commercialization of LONSURF. Under the terms of the agreement, Servier will commercialize LONSURF in Europe and other regions outside of the United States, Canada, Mexico and Asia. The application is currently under review by the European Commission after the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) where a positive opinion was adopted on February 25, recommending the granting of a marketing authorization for LONSURF (R) (trifluridine/tipiracil) for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti EGFR agents. (*4) LONSURF is an oral combination anticancer drug of trifluridine (FTD) and tipiracil (TPI). FTD is a thymidine-based nucleoside analog, which is incorporated directly into DNA, thereby interfering with DNA synthesis and inhibits cell proliferation. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.
Important Safety Information (*5)
WARNINGS AND PRECAUTIONS
Severe Myelosuppression: In Study 1, LONSURF (R) (trifluridine and tipiracil) caused severe and life-threatening myelosuppression (Grade 3-4) consisting of anemia (18%), neutropenia (38%), thrombocytopenia (5%), and febrile neutropenia (3.8%). One patient (0.2%) died due to neutropenic infection. In Study 1, 9.4% of LONSURF-treated patients received granulocyte-colony stimulating factors.
Obtain complete blood counts prior to and on day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for febrile neutropenia, Grade 4 neutropenia, or platelets less than 50,000/mm3. Upon recovery, resume LONSURF at a reduced dose.
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 |
SOURCE: Taiho Pharmaceutical Co
