PRINCETON, N.J., June 21, 2018 /PRNewswire/ -- Taiho Oncology,
Inc. and Servier today announced clinical data from the pivotal
Phase III trial (TAGS) evaluating LONSURF® (trifluridine and
tipiracil, TAS-102) plus best supportive care (BSC) versus placebo
plus BSC in patients with previously treated metastatic gastric
cancer refractory to standard therapies. This trial met its primary
endpoint of overall survival (OS) and secondary endpoint measures
of progression-free survival (PFS), and safety and tolerability, as
well as quality of life. The data were presented as oral and poster
presentations at the ESMO 20th World Congress on Gastrointestinal
Cancer 2018 (ESMO-GI) in Barcelona,
Spain, June 20 to 23.
In the TAGS trial, patients treated with LONSURF had a 31% risk
reduction of death and a prolongation of their median survival by
2.1 months when compared with placebo (OS of 5.7 months compared to
3.6 months in the placebo group (hazard ratio [HR]: 0.69; 95%
confidence interval [CI] 0.56, 0.85; one-sided p=0.0003); at
12-months, OS rates were 21.2% in the LONSURF group and 13.0% in
the placebo group. In addition, the risk for disease progression as
measured by PFS, a key secondary endpoint, was reduced by 43% (HR:
0.57).
Any Grade 3 or higher adverse events (AEs) occurred in 80% of
treated patients who received LONSURF and in 58% of treated
patients who received placebo. Grade 3/4 hematological AEs in
patients treated with trifluridine and tipiracil included
neutropenia (38%), leucopenia (21%), anemia (19%) and
lymphocytopenia (19%). Of the 38% of patients who experienced grade
3/4 neutropenia when treated with LONSURF, six (2%) experienced
febrile neutropenia. No new safety signals were observed for
LONSURF in the TAGS study.
"We are excited to be able to share these important data with
the medical oncology community and to continue to add to the
growing body of research supporting the efficacy and safety of
LONSURF," said Martin J. Birkhofer,
MD, senior vice president and Chief Medical Officer, Taiho Oncology, Inc. "We intend to include these
data in an sNDA submission to the U.S. Food and Drug Administration
(FDA) for consideration as a third-line treatment option for
appropriate patients with metastatic gastric cancer."
LONSURF is currently indicated in the
United States for the treatment of patients with metastatic
colorectal cancer 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.1
"These results provide a potential new treatment option to
patients with advanced gastric cancer," said Professor Josep Tabernero, MD, PhD, MSc, head of the
Medical Oncology Department at the Vall d'Hebron Barcelona Hospital
Campus, director of the Vall d'Hebron Institute of Oncology (VHIO),
and primary investigator on the TAGS trial. "We are grateful to the
patients, caregivers and physician investigators for their
participation in this important clinical study."
The abstract for this presentation is available on the ESMO-GI
website at http://sched.co/DrlV.
About TAGS
The TAGS (TAS-102 Gastric
Study) trial is a Taiho-sponsored pivotal Phase III
multinational, randomized, double-blind study evaluating LONSURF®
(trifluridine and tipiracil), also known as TAS-102, plus best
supportive care (BSC) versus placebo plus BSC in patients with
metastatic gastric cancer refractory to standard treatments. The
primary endpoint in the TAGS trial is overall survival (OS), and
secondary endpoint measures include progression-free survival
(PFS), and safety and tolerability, as well as quality of life.
The TAGS trial aimed to enroll 500 adults 18 years and older
with metastatic gastric cancer who had previously received at least
two prior regimens for advanced disease. The trial enrolled 507
subjects and was conducted in Japan, North
America, Europe,
Russia and Turkey, among other locations.
For more information on the TAGS trial, please visit
www.ClinicalTrials.gov
(https://clinicaltrials.gov/ct2/show/NCT02500043). The
ClinicalTrials.gov Identifier is NCT02500043.
About Metastatic Colorectal Cancer
Colorectal cancer is the third most common type of cancer,
excluding skin cancers, in the United
States, with an estimated 135,430 new patients diagnosed in
2017.2 It is the second and third leading cause of
cancer-related deaths among men and women,
respectively.2
Colorectal cancers that have spread to other parts of the body
are often harder to treat and tend to have a poorer
outlook.3 Metastatic, or stage IV colon and rectal
cancers, have a five-year relative survival rate of about 11% and
12%, respectively.3 Still, there are often many
treatment options available for people with this stage of
cancer.3 Further, treatments have improved over the last
few decades.3 As a result, there are now more than one
million survivors of colorectal cancer in the United States.3
About Metastatic Gastric Cancer
Gastric cancer, also known as stomach cancer, is a disease in which
malignant cells form in the lining of the stomach. It 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.4 Approximately 50% of
patients with gastric cancer have advanced disease at the time of
diagnosis.5
Standard chemotherapy regimens for advanced gastric cancer
include fluoropyrimidines, platinum derivatives, and taxanes (with
Ramucirumab), or irinotecan. The addition of trastuzumab to
chemotherapy is standard of care for patients with
HER2-neu-positive advanced gastric cancer. However, after failure
of first- and second-line therapies, standard third-line treatments
are limited.
About LONSURF (TAS-102)
LONSURF is an oral combination of trifluridine, a nucleoside
metabolic inhibitor, and tipiracil, a thymidine phosphorylase
inhibitor, anticancer drug indicated in United States for the treatment of patients
with metastatic colorectal cancer (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.1 LONSURF is also
available in EU,6 Japan, and other countries.
In June 2015, Taiho Pharmaceutical
Co., Ltd. entered into an exclusive license agreement with Servier
for the co-development and commercialization of LONSURF. Under the
terms of the agreement, Taiho Pharmaceutical Co., Ltd. granted
Servier the right to co-develop and commercialize LONSURF in
Europe and other countries outside
of the United States, Canada, Mexico and Asia. Taiho Pharmaceutical Co., Ltd. retains
the right to develop and commercialize LONSURF in the United States, Canada, Mexico, and Asia and to manufacture and supply the
product.
Important Safety Information1
WARNINGS AND PRECAUTIONS
Severe Myelosuppression: In RECOURSE Study, LONSURF
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 as clinically indicated.
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%).
Hepatic Impairment: Patients with severe hepatic
impairment (total bilirubin greater than 3 times ULN and any AST)
were not studied. No adjustment to the starting dose of LONSURF is
recommended for patients with mild hepatic impairment. Do not
initiate LONSURF in patients with baseline moderate or severe
(total bilirubin greater than 1.5 times ULN and any AST) hepatic
impairment.
Renal Impairment: In RECOURSE Study, patients with
moderate renal impairment (CLcr=30 to 59 mL/min, n=47) had a higher
incidence (difference of at least 5%) of ≥Grade 3 adverse events,
serious adverse events, and dose delays and reductions compared to
patients with normal renal function (CLcr ≥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. Patients with severe renal
impairment were not studied.
ADVERSE REACTIONS
Most Common Adverse Drug Reactions in Patients Treated With
LONSURF
(≥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 US Prescribing Information.
www.taihooncology.com/us/prescribing-information.pdf.
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 with a strong commercial business
in the U.S. dedicated to bringing the company's approved medical
innovations to patients. Taiho 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:
https://www.taihooncology.com.
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, allergy
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, a reputation that is rapidly
expanding through their extensive global R&D efforts. In areas
other than oncology, as well, the company creates and markets
quality products that effectively treat medical conditions and can
help improve people's quality of life. Always putting customers
first, Taiho Pharmaceutical also aims to offer consumer healthcare
products that support people's efforts to lead fulfilling and
rewarding lives.
For more information about Taiho Pharmaceutical, please visit:
https://www.taiho.co.jp/en/.
About Otsuka Holdings Co., Ltd. (Japan)
The Otsuka group of companies is a total-healthcare enterprise that
aims to contribute to the health of people around world under the
corporate philosophy, "Otsuka-people creating new products for
better health worldwide."
Healthcare is broadly and holistically addressed through the two
main pillars – the pharmaceutical business for the diagnosis and
treatment of diseases and the nutraceutical1 business to
support the maintenance and promotion of everyday health. Our
46,0002 employees across 183 companies in 28 countries
and regions take on challenges across various fields and themes to
help fulfill the universal wish of people to be healthy. Our
pursuit of these challenges is motivated by the Otsuka' s corporate
culture, articulated as "Ryukan-godo" (by sweat we recognize the
way), "Jissho" (actualization) and "Sozosei" (creativity), and
fostered by successive generations of Otsuka leaders. By striving
to provide unique products and services, we seek to achieve
sustainable growth and be an indispensable contributor to the
world.
For more information, please visit the company's website at
https://www.otsuka.com/en/.
____________________
1 Nutraceuticals: nutrition +
pharmaceuticals
2 As of end of December
2017
About Servier
Servier is an international pharmaceutical company governed by a
non-profit foundation, with its headquarters in France (Suresnes). With a strong international
presence in 148 countries and a turnover of 4.152 billion euros in 2017, Servier employs
21,600 people worldwide. Entirely independent, the Group reinvests
25 percent of its turnover (excluding generic drugs) in research
and development and uses all its profits for development. Corporate
growth is driven by Servier's constant search for innovation in
five areas of excellence: cardiovascular, immune-inflammatory and
neuropsychiatric diseases, cancer and diabetes, as well as by its
activities in high-quality generic drugs.
Becoming a key player in oncology is part of Servier's long-term
strategy. Currently, there are nine molecular entities in clinical
development in this area, targeting gastric and lung cancers and
other solid tumors, as well as different types of leukemia and
lymphomas. This portfolio of innovative cancer treatments is being
developed with partners worldwide, and covers different cancer
hallmarks and modalities, including cytotoxics, proapoptotics,
immune, cellular and targeted therapies, to deliver life-changing
medicines to patients. Servier also offers eHealth solutions beyond
drug development.
For more information about Servier, please visit
www.servier.com.
U.S. Media Contact:
Craig Heit
GCI Health on behalf of Taiho Oncology
Taihooncology@gcihealth.com
212-798-9919
E.U. Servier Media Contact:
Sonia Marques
Media@servier.com
+33 (0)1 55 72 40 21 / + 33 (0) 7 84 28 76 13
Karine Bousseau
Media@servier.com
+33 (0)1 55 72 60 37
____________________
1 LONSURF [US prescribing information]; Princeton, NJ: Taiho Oncology, Inc.; 2017.
2017.
2 American Cancer Society; What are the key statistics
about colorectal cancer?
http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-key-statistics.
Accessed December 2017.
3 American Cancer Society; What Are the Survival Rates
for Colorectal Cancer, by Stage?
https://www.cancer.org/cancer/colon-rectal-cancer/detection-diagnosis-staging/survival-rates.html.
Accessed December 2017.
4 Ferlay J, Soerjomataram I, Dikshit R, et al. Int J
Cancer. 2015;136:E359-86.
5 National Comprehensive Cancer Network (NCCN). Clinical
Practice Guidelines in Oncology. Gastric cancer. Version 2.2018.
http://www.nccn.org. Accessed June 2018.
6 Lonsurf EU Summary of Product Characteristics (SmPC);
August 2017:
http://www.ema.europa.eu/ema/. Accessed June
2018.
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