WHIPPANY, N.J., April 27, 2017 /PRNewswire/ --
WARNING: HEPATOTOXICITY
- Severe and sometimes fatal hepatotoxicity has occurred in
clinical trials.
- Monitor hepatic function prior to and during
treatment.
- Interrupt and then reduce or discontinue STIVARGA for
hepatotoxicity as manifested by elevated liver function tests or
hepatocellular necrosis, depending upon severity and
persistence.
Bayer announced today that the U.S. Food and Drug Administration
(FDA) approved Stivarga® (regorafenib) tablets for the
second-line treatment of patients with hepatocellular carcinoma
(HCC) who have been previously treated with Nexavar®
(sorafenib).2 Stivarga is the first and only treatment
to demonstrate significant improvement in overall survival in
second-line HCC patients.2 In the RESORCE trial,
Stivarga was shown to provide a statistically significant and
clinically meaningful improvement in overall survival (OS) versus
placebo; the median OS was 10.6 [(n=379) (CI 9.1, 12.1)] vs 7.8
[(n=194) (CI 6.3, 8.8)] months, respectively (HR 0.63, 95% CI
0.50-0.79; p<0.0001).2 This translates to a 37%
reduction in the risk of death. The number of deaths in each arm
included 233 of 379 (62%) with Stivarga and 140 of 194 (72%) with
placebo.2 Today's FDA approval expands Bayer's
leadership in liver cancer with a treatment plan in HCC involving
use of Stivarga directly after progression on
Nexavar.2
Experience the interactive Multimedia News Release here:
https://www.multivu.com/players/English/8002351-bayer-stivarga-fda-approval/
Stivarga is an oral inhibitor of multiple kinases involved in
normal cellular functioning and in pathological processes such as
oncogenesis, tumor angiogenesis, metastasis and tumor
immunity.2 The FDA's approval is based on data from the
international, multicenter, placebo-controlled Phase III RESORCE
[REgorafenib after SORafenib in patients with hepatoCEllular
carcinoma; NCT 01774344] trial, which investigated patients with
HCC whose disease had progressed during treatment with
Nexavar.2 The most frequently observed adverse
drug reactions (≥30%) in STIVARGA-treated patients vs
placebo-treated patients in HCC, respectively, were: pain (55% vs
44%), HFSR/PPE (51% vs 7%), pain (55% vs 44%), asthenia/fatigue
(42% vs 33%), diarrhea (41% vs 15%), hypertension (31% vs 6%),
infection (31% vs 18%), decreased appetite and food intake (31% vs
15%).2
"Bayer is proud to have played a significant role in the
treatment of hepatocellular carcinoma," said Robert LaCaze, executive vice president and head
of the Oncology Strategic Business Unit at Bayer. "We first
embarked on our scientific research in this area 20 years ago and
we have remained steadfast in our mission to deliver new treatment
options to these patients. We could not have done it alone: we
would like to thank the patients, caregivers and investigators for
their participation and engagement in the study."
Thomas F. Nealon III, national
board chair and chief executive officer of the American Liver
Foundation, commented, "Given that the incidence of liver cancer
continues to rise,3 we applaud the efforts of Bayer and
the RESORCE study investigators for ushering in this much-needed
treatment option for patients with liver cancer."
The approval of Stivarga in liver cancer marks the third time
that this therapy has been granted FDA approval on a priority
basis. The FDA granted Fast Track designation to Stivarga in this
indication, which is an expedited program designed to facilitate
development and review of drugs to address unmet medical need in
the treatment of a serious or life-threatening condition. The FDA
also granted Orphan Drug Designation (ODD) to Stivarga in HCC. The
ODD program provides orphan status to drugs and biologics which are
defined as those intended for the safe and effective treatment,
diagnosis or prevention of rare diseases and disorders.
Additional regulatory filings for Stivarga in HCC are under
review in countries around the world, including the EU,
Japan and China. Decisions in the EU and Japan are expected later in this year.
About Hepatocellular Carcinoma
Hepatocellular
carcinoma (HCC) is the most common form of liver cancer and
represents approximately three quarters of liver cancers in
the United States.4 It
is estimated that more than 40,000 people in the U.S. will be
diagnosed with liver cancer in 2017.4 Liver cancer is
still on the rise and death rates are increasing faster than any
other type of cancer.3 In the
United States, the incidence of liver cancer has more than
tripled since 1980 and nearly 29,000 deaths from liver cancer are
expected in 2017.4 In 2012, 782,000 men and women were
diagnosed with liver cancer and approximately 746,000 people died
of liver cancer worldwide.5 Globally, it is the second
leading cause of cancer-related deaths.5
About Stivarga® (regorafenib)
In
April 2017, Stivarga was approved for
use in patients with hepatocellular carcinoma who have been
previously treated with Nexavar.2 In the United States, Stivarga is also indicated
for the treatment of patients with metastatic colorectal cancer
(CRC) who have been previously treated with fluoropyrimidine-,
oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF
therapy, and, if RAS wild-type, an anti-EGFR therapy. It is also
indicated for the treatment of patients with locally advanced,
unresectable or metastatic gastrointestinal stromal tumor (GIST)
who have been previously treated with imatinib mesylate and
sunitinib malate.2
Regorafenib is a compound developed by Bayer. In 2011, Bayer
entered into an agreement with Onyx, now an Amgen subsidiary, under
which Onyx receives a royalty on all global net sales of
regorafenib in oncology.
Important Safety Information
WARNING: HEPATOTOXICITY
- Severe and sometimes fatal hepatotoxicity has occurred in
clinical trials.
- Monitor hepatic function prior to and during
treatment.
- Interrupt and then reduce or discontinue STIVARGA for
hepatotoxicity as manifested by elevated liver function tests or
hepatocellular necrosis, depending upon severity and
persistence.
Hepatotoxicity: Severe drug-induced liver injury with
fatal outcome occurred in STIVARGA-treated patients across all
clinical trials. In most cases, liver dysfunction occurred within
the first 2 months of therapy and was characterized by a
hepatocellular pattern of injury. In metastatic colorectal cancer
(mCRC), fatal hepatic failure occurred in 1.6% of patients in the
STIVARGA arm and in 0.4% of patients in the placebo arm. In
gastrointestinal stromal tumor (GIST), fatal hepatic failure
occurred in 0.8% of patients in the STIVARGA arm. In hepatocellular
carcinoma (HCC), there was no increase in the incidence of fatal
hepatic failure as compared to placebo.
Liver Function Monitoring: Obtain liver function tests
(ALT, AST, and bilirubin) before initiation of STIVARGA and monitor
at least every 2 weeks during the first 2 months of treatment.
Thereafter, monitor monthly or more frequently as clinically
indicated. Monitor liver function tests weekly in patients
experiencing elevated liver function tests until improvement to
less than 3 times the upper limit of normal (ULN) or baseline
values. Temporarily hold and then reduce or permanently discontinue
STIVARGA, depending on the severity and persistence of
hepatotoxicity as manifested by elevated liver function tests or
hepatocellular necrosis.
Infections: STIVARGA caused an increased risk of
infections. The overall incidence of infection (Grades 1-5) was
higher (32% vs 17%) in 1142 STIVARGA-treated patients as compared
to the control arm in randomized placebo-controlled trials. The
incidence of grade 3 or greater infections in STIVARGA treated
patients was 9%. The most common infections were urinary tract
infections (5.7%), nasopharyngitis (4.0%), mucocutaneous and
systemic fungal infections (3.3%) and pneumonia (2.6%). Fatal
outcomes caused by infection occurred more often in patients
treated with STIVARGA (1.0%) as compared to patients receiving
placebo (0.3%); the most common fatal infections were respiratory
(0.6% vs 0.2%). Withhold STIVARGA for Grade 3 or 4 infections, or
worsening infection of any grade. Resume STIVARGA at the same dose
following resolution of infection.
Hemorrhage: STIVARGA caused an increased incidence of
hemorrhage. The overall incidence (Grades 1-5) was 18.2% in 1142
patients treated with STIVARGA vs 9.5% with placebo in randomized,
placebo-controlled trials. The incidence of grade 3 or greater
hemorrhage in patients treated with STIVARGA was 3.0%. The
incidence of fatal hemorrhagic events was 0.7%, involving the
central nervous system or the respiratory, gastrointestinal, or
genitourinary tracts. Permanently discontinue STIVARGA in patients
with severe or life-threatening hemorrhage and monitor INR levels
more frequently in patients receiving warfarin.
Gastrointestinal Perforation or Fistula: Gastrointestinal
perforation occurred in 0.6% of 4518 patients treated with STIVARGA
across all clinical trials of STIVARGA administered as a single
agent; this included eight fatal events. Gastrointestinal fistula
occurred in 0.8% of patients treated with STIVARGA and in 0.2% of
patients in the placebo arm across randomized, placebo-controlled
trials. Permanently discontinue STIVARGA in patients who develop
gastrointestinal perforation or fistula.
Dermatological Toxicity: In randomized,
placebo-controlled trials, adverse skin reactions occurred in 71.9%
of patients with STIVARGA arm and 25.5% of patients in the placebo
arm including hand-foot skin reaction (HFSR) also known as
palmar-plantar erythrodysesthesia syndrome (PPES) and severe rash,
requiring dose modification. In the randomized, placebo-controlled
trials, the overall incidence of HFSR was higher in 1142
STIVARGA-treated patients (53% vs 8%) than in the placebo-treated
patients. Most cases of HFSR in STIVARGA-treated patients appeared
during the first cycle of treatment. The incidences of Grade 3 HFSR
(16% vs <1%), Grade 3 rash (3% vs <1%), serious adverse
reactions of erythema multiforme (<0.1% vs 0%), and
Stevens-Johnson syndrome (<0.1% vs 0%) were higher in
STIVARGA-treated patients. Across all trials, a higher incidence of
HFSR was observed in Asian patients treated with STIVARGA (all
grades: 72%; Grade 3:18%). Toxic epidermal necrolysis occurred in
0.02% of 4518 STIVARGA-treated patients across all clinical trials
of STIVARGA administered as a single agent. Withhold STIVARGA,
reduce the dose, or permanently discontinue depending on the
severity and persistence of dermatologic toxicity.
Hypertension: Hypertensive crisis occurred in 0.2% in
STIVARGA-treated patients and in none of the patients in placebo
arm across all randomized, placebo-controlled trials. STIVARGA
caused an increased incidence of hypertension (30% vs 8% in mCRC,
59% vs 27% in GIST, and 31% vs 6% in HCC). The onset of
hypertension occurred during the first cycle of treatment in most
patients who developed hypertension (67% in randomized, placebo
controlled trials). Do not initiate STIVARGA until blood pressure
is adequately controlled. Monitor blood pressure weekly for the
first 6 weeks of treatment and then every cycle, or more
frequently, as clinically indicated. Temporarily or permanently
withhold STIVARGA for severe or uncontrolled hypertension.
Cardiac Ischemia and Infarction: STIVARGA increased the
incidence of myocardial ischemia and infarction (0.9% with STIVARGA
vs 0.2% with placebo) in randomized placebo-controlled trials.
Withhold STIVARGA in patients who develop new or acute cardiac
ischemia or infarction, and resume only after resolution of acute
cardiac ischemic events if the potential benefits outweigh the
risks of further cardiac ischemia.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
Reversible posterior leukoencephalopathy syndrome (RPLS), a
syndrome of subcortial vasogenic edema diagnosed by characteristic
finding on MRI occurred in one of 4800 STIVARGA-treated patients
across all clinical trials. Perform an evaluation for RPLS in any
patient presenting with seizures, severe headache, visual
disturbances, confusion, or altered mental function. Discontinue
STIVARGA in patients who develop RPLS.
Wound Healing Complications: Treatment with STIVARGA
should be stopped at least 2 weeks prior to scheduled surgery.
Resuming treatment after surgery should be based on clinical
judgment of adequate wound healing. STIVARGA should be discontinued
in patients with wound dehiscence.
Embryo-Fetal Toxicity: STIVARGA can cause fetal harm when
administered to a pregnant woman. There are no available data on
STIVARGA use in pregnant women. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential
and males with female partners of reproductive potential to use
effective contraception during treatment with STIVARGA and for 2
months after the final dose.
Nursing Mothers: Because of the potential for serious
adverse reactions in breastfed infants from STIVARGA, do not
breastfeed during treatment with STIVARGA and for 2 weeks after the
final dose.
Most Frequently Observed Adverse Drug Reactions in
mCRC (≥30%): The most frequently observed adverse drug
reactions (≥30%) in STIVARGA-treated patients vs placebo-treated
patients in mCRC, respectively, were: asthenia/fatigue (64% vs
46%), pain (59% vs 48%), decreased appetite and food intake (47% vs
28%), HFSR/PPE (45% vs 7%), diarrhea (43% vs 17%), mucositis (33%
vs 5%), weight loss (32% vs 10%), infection (31% vs 17%),
hypertension (30% vs 8%), and dysphonia (30% vs 6%).
Most Frequently Observed Adverse Drug Reactions in GIST
(≥30%): The most frequently observed adverse drug reactions
(≥30%) in STIVARGA-treated patients vs placebo-treated patients in
GIST, respectively, were: HFSR/PPE (67% vs 12%), pain (60% vs 55%),
hypertension (59% vs 27%), asthenia/fatigue (52% vs 39%), diarrhea
(47% vs 9%), mucositis (40% vs 8%), dysphonia (39% vs 9%),
infection (32% vs 5%), decreased appetite and food intake (31% vs
21%), and rash (30% vs 3%).
Most Frequently Observed Adverse Drug Reactions in HCC
(≥30%):
The most frequently observed adverse drug reactions (≥30%) in
STIVARGA-treated patients vs placebo-treated patients in HCC,
respectively, were: pain (55% vs 44%), HFSR/PPE (51% vs 7%),
asthenia/fatigue (42% vs 33%), diarrhea (41% vs 15%), hypertension
(31% vs 6%), infection (31% vs 18%), decreased appetite and food
intake (31% vs 15%).
Please see full Prescribing Information, including Boxed
Warning.
About Oncology at Bayer
Bayer is
committed to delivering science for a better life by advancing a
portfolio of innovative treatments. Bayer is a global leader in the
management and treatment of hepatocellular carcinoma. The oncology
franchise at Bayer includes three oncology products and several
other compounds in various stages of clinical development.
Together, these products reflect the company's approach to
research, which prioritizes targets and pathways with the potential
to impact the way that cancer is treated.
Bayer: Science For A Better Life
Bayer is a global
enterprise with core competencies in the Life Science fields of
health care and agriculture. Its products and services are designed
to benefit people and improve their quality of life. At the same
time, the Group aims to create value through innovation, growth and
high earning power. Bayer is committed to the principles of
sustainable development and to its social and ethical
responsibilities as a corporate citizen. In fiscal 2016, the Group
employed around 115,200 people and had sales of EUR 46.8 billion. Capital expenditures amounted
to EUR 2.6 billion, R&D expenses
to EUR 4.7 billion. These figures
include those for the high-tech polymers business, which was
floated on the stock market as an independent company named
Covestro on October 6, 2015. For more
information, go to www.bayer.us.
© 2017 Bayer
BAYER, the Bayer Cross, Stivarga and Nexavar are registered
trademarks of Bayer.
Media Contact:
Rose
Talarico, Tel. +1 862.404.5302
E-Mail: rose.talarico@bayer.com
Forward-Looking Statement
This news release may
contain forward-looking statements based on current assumptions and
forecasts made by Bayer Group or subgroup management. Various known
and unknown risks, uncertainties and other factors could lead to
material differences between the actual future results, financial
situation, development or performance of the company and the
estimates given here. These factors include those discussed in
Bayer's public reports which are available on the Bayer website at
www.bayer.com. The company assumes no liability whatsoever to
update these forward-looking statements or to conform them to
future events or developments.
- U.S. Food and Drug Administration website.
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm555608.htm.
Accessed April 2017.
- STIVARGA® (regorafenib) [Prescribing Information].
Whippany, NJ: Bayer HealthCare
Pharmaceuticals, April 2017.
- Ryerson, A. B., et al (2016), Annual Report to the Nation on
the Status of Cancer, 1975-2012, featuring the increasing incidence
of liver cancer. Cancer, 122: 1312–1337. doi:10.1002/cncr.29936.
https://seer.cancer.gov/report_to_nation/. Accessed April 2017.
- American Cancer Society. Liver Cancer. 2017.
https://www.cancer.org/cancer/liver-cancer.html. Accessed
April 2017.
- GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and
Prevalence Worldwide in 2012.
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed
April 2017.
PP-550-US-0528
Intended for U.S. Media Only
SOURCE Bayer