WOODCLIFF LAKE, N.J.,
Sept. 29, 2016 /PRNewswire/
-- Eisai Inc. announced today the presentation of seven
abstracts featuring data on its cancer treatments at the European
Society of Medical Oncology (ESMO) 2016 Congress. The abstracts
highlight new results for the company's oncology agents,
Halaven® (eribulin) and Lenvima®
(lenvatinib), for investigational uses in difficult-to-treat
cancers and provide new information about these agents across
multiple tumor types. ESMO 2016 will be held from October 7-11 in Copenhagen, Denmark.
"The breadth of data to be presented at ESMO—from interim
results from the Phase 1b portion of our trial evaluating
lenvatinib in combination with the anti-PD-1 immunotherapy
pembrolizumab to results from multiple sub-group analyses of
registrational studies for eribulin and lenvatinib—underscores
Eisai's commitment to researching and developing treatment options
for patients with advanced cancers," said Alton Kremer, MD, PhD, Chief Clinical Officer
and Chief Medical Officer, Oncology Business Group at Eisai. "We
are continually looking to improve understanding of Eisai's
oncology therapies, and through these data, we hope to support the
medical community and the patients we both serve."
Presentations of note include:
- Studies assessing the use of lenvatinib in combination with
anti-PD-1 immunotherapy, including:
- Initial results of an ongoing, open-label, multicenter, Phase
1b trial of lenvatinib in combination with pembrolizumab in
patients with select solid tumors
- A preclinical study analyzing the immune response in mouse
tumor models to understand the anti-tumor effect and mechanism of
action of the combination of lenvatinib and PD-1 blockade treatment
in multiple cancer types
- Sub-analyses of the Phase 3 SELECT study investigating
responses in specific sites of metastasis (lung, liver, lymph nodes
and bone) following treatment with lenvatinib for locally recurrent
or metastatic, progressive, radioactive iodine-refractory
differentiated thyroid cancer
- A preclinical study analyzing the role of FGFR and VEGFR
signaling pathways in tumor growth and angiogenesis in human renal
cell carcinoma xenografts treated with lenvatinib in combination
with everolimus
Abstract
Name
|
Session (All
times are CEST)
|
Lenvima
Abstracts
|
Responses in
specific metastases following treatment with lenvatinib: results
from the Phase 3 SELECT Study
|
Abstract
#2038
Poster
Display
Sunday, October 9,
2016, 13:00 - 14:00 CEST
Location: Hall
E
B.
Robinson
|
Understanding real
world treatment patterns, healthcare resource utilization (HRU) and
costs among metastatic renal cell carcinoma (mRCC)
patients
|
Abstract
#2616
Poster
Display
Sunday, October 9,
2016, 13:00 - 14:00 CEST
Location: Hall
E
R. Copher
|
Phase 2 study of
lenvatinib in patients with RET fusion-positive adenocarcinoma of
the lung
|
Abstract
#1608
Poster Discussion
Session
Sunday, October 9,
2016, 14:45 - 16:15 CEST
Location:
Oslo
V.
Velcheti
To be discussed at
the Poster Discussion Session on Sunday, October 9, 2016, 14:45
- 15:02 CEST
|
A phase 1b trial
of lenvatinib plus pembrolizumab in patients with selected solid
tumors
|
Abstract
#1779
Poster Discussion
Session
Sunday, October 9,
2016, 16:30 - 17:30 CEST
Location:
Athens
To be discussed at
the Poster Discussion Session on Sunday, October 9, 2016, 16:30
- 16:50 CEST
|
Lenvatinib
mesilate enhanced antitumor activity of a PD-1 blockade agent by
potentiating Th1 immune response
|
Abstract
#2008
Poster Discussion
Session
Sunday, October 9,
2016, 16:30 - 17:30 CEST
Location:
Berlin
Y. Kato
To be discussed at
the Poster Discussion Session on Sunday, October 9, 2016, 17:10
- 17:30 CEST
|
The antitumor
activity of lenvatinib in combination with everolimus in human
renal cell carcinoma xenograft models is dependent on the VEGFR and
FGFR signaling
|
Abstract
#1284
Poster
Display
Monday, October 10,
2016, 13:00 - 14:00 CEST
Location: Hall
E
T. Kimura
|
Halaven
Abstract
|
Subgroup analysis
in leiomyosarcoma (LMS) patients from a Phase 3, open-label,
randomized study of eribulin versus dacarbazine in pts with
advanced liposarcoma and LMS
|
Abstract
#1879
Poster Discussion
Session
Monday, October 10,
2016, 11:00 - 12:00 CEST
Location:
Brussels
J.-Y. Blay
To be discussed at
the Poster Discussion Session on Monday, October 10, 2016,
11:20 - 11:40 CEST
|
This release discusses investigational uses for FDA-approved
products. It is not intended to convey conclusions about efficacy
and safety. There is no guarantee that any investigational uses of
FDA-approved products will successfully complete clinical
development or gain FDA approval.
About LENVIMA®
(lenvatinib)
LENVIMA® (lenvatinib) is a kinase
inhibitor that is indicated for:
- Differentiated Thyroid Cancer (DTC): single agent for patients
with locally recurrent or metastatic, progressive, radioactive
iodine-refractory DTC.
- Renal Cell Cancer (RCC): in combination with everolimus for
patients with advanced RCC following one prior anti-angiogenic
therapy.
Lenvatinib, discovered and developed by Eisai, is a multiple
receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase
activities of vascular endothelial growth factor (VEGF) receptors
VEGFR1-3. Lenvatinib also inhibits other RTKs that have been
implicated in pathogenic angiogenesis, tumor growth, and cancer
progression in addition to their normal cellular functions,
including fibroblast growth factor (FGF) receptors FGFR1-4; the
platelet derived growth factor receptor alpha (PDGFRα), KIT, and
RET. The combination of lenvatinib and everolimus showed increased
anti-angiogenic and anti-tumor activity as demonstrated by
decreased human endothelial cell proliferation, tube formation, and
VEGF signaling in vitro and tumor volume in mouse xenograft
models of human renal cell cancer greater than each drug alone.
Important Safety Information
Warnings and Precautions
- In DTC, hypertension was reported in 73% of patients on LENVIMA
vs 16% with placebo (44% vs 4% grade ≥3). In RCC, hypertension was
reported in 42% of patients on LENVIMA + everolimus vs 10% with
everolimus alone (13% vs 2% grade 3). Blood pressure should be
controlled prior to treatment and monitored throughout. Withhold
dose for grade 3 hypertension despite optimal antihypertensive
therapy; resume at reduced dose when controlled at grade ≤2.
Discontinue for life-threatening hypertension
- In DTC, cardiac dysfunction was reported in 7% of patients on
LENVIMA vs 2% with placebo (2% vs 0% grade ≥3). In RCC, cardiac
dysfunction was reported in 10% of patients on LENVIMA + everolimus
vs 6% with everolimus alone (3% vs 2% grade 3). Monitor for
signs/symptoms of cardiac decompensation. Withhold for grade 3
cardiac dysfunction. Resume at reduced dose or discontinue based on
severity and persistence of cardiac dysfunction. Discontinue for
grade 4 cardiac dysfunction
- In DTC, arterial thromboembolic events were reported in 5% of
patients on LENVIMA vs 2% with placebo (3% vs 1% grade ≥3). In RCC,
arterial thromboembolic events were reported in 2% of patients on
LENVIMA + everolimus vs 6% with everolimus alone (2% vs 4% grade
≥3). Discontinue following an arterial thrombotic event. The safety
of resuming LENVIMA after an arterial thromboembolic event has not
been established, and LENVIMA has not been studied in patients who
have had an arterial thromboembolic event within the previous 6
months
- Across clinical studies in which 1,160 patients received
LENVIMA monotherapy, hepatic failure (including fatal events) was
reported in 3 patients and acute hepatitis in 1 patient. In DTC,
ALT and AST increases (grade ≥3) occurred in 4% and 5% of patients
on LENVIMA, respectively, vs 0% with placebo. In RCC, ALT and AST
increases (grade ≥3) occurred in 3% of patients on LENVIMA +
everolimus vs 2% and 0% with everolimus alone, respectively.
Monitor liver function before initiation, then every 2 weeks for
the first 2 months, and at least monthly thereafter during
treatment. Withhold dose for liver impairment grade ≥3 until
resolved to grade 0, 1, or baseline. Resume at reduced dose or
discontinue based on severity/persistence of hepatotoxicity.
Discontinue for hepatic failure
- In DTC, proteinuria was reported in 34% of patients on LENVIMA
vs 3% with placebo (11% vs 0% grade 3). In RCC, proteinuria was
reported in 31% of patients on LENVIMA + everolimus vs 14% with
everolimus alone (8% vs 2% grade 3). Monitor for proteinuria before
and during treatment. Withhold dose for proteinuria ≥2 g/24 h.
Resume at reduced dose when proteinuria is <2 g/24 h.
Discontinue for nephrotic syndrome
- In RCC, diarrhea was reported in 81% of patients on LENVIMA +
everolimus vs 34% with everolimus alone (19% vs 2% grade ≥3).
Initiate prompt medical management for the development of diarrhea.
Monitor for dehydration. Withhold dose for diarrhea grade ≥3.
Resume at a reduced dose when diarrhea resolves to grade 1 or
baseline. Discontinue for grade 4 diarrhea despite medical
management
- In DTC, events of renal impairment were reported in 14% of
patients on LENVIMA vs 2% with placebo (3% vs 1% grade ≥3). In RCC,
events of renal impairment were reported in 18% of patients on
LENVIMA + everolimus vs 12% with everolimus alone (10% vs 2% grade
≥3). Withhold LENVIMA for grade 3 or 4 renal failure/impairment.
Resume at reduced dose or discontinue, depending on
severity/persistence of renal impairment. Active management of
diarrhea and any other gastrointestinal (GI) symptoms should be
initiated for grade 1 events
- In DTC, events of GI perforation or fistula were reported in 2%
of patients on LENVIMA vs 0.8% with placebo. In RCC, events of GI
perforation, abscess, or fistula (grade ≥3) were reported in 2% of
patients on LENVIMA + everolimus vs 0% with everolimus alone.
Discontinue in patients who develop GI perforation or
life-threatening fistula
- In DTC, QT/QTc interval prolongation was reported in 9% of
patients on LENVIMA vs 2% with placebo (2% vs 0% >500 ms). In
RCC, QTc interval increases >60 ms were reported in 11% of
patients on LENVIMA + everolimus (6% >500 ms) vs 0% with
everolimus alone. Monitor electrocardiograms in patients with
congenital long QT syndrome, congestive heart failure,
bradyarrhythmias, or patients taking drugs known to prolong the QT
interval. Monitor and correct electrolyte abnormalities in all
patients. Withhold dose for QTc interval prolongation >500 ms.
Resume at reduced dose when QTc prolongation resolves to
baseline
- In DTC, hypocalcemia (grade ≥3) was reported in 9% of patients
on LENVIMA vs 2% with placebo. In RCC, hypocalcemia (grade ≥3) was
reported in 6% of patients on LENVIMA + everolimus vs 2% with
everolimus alone. Monitor blood calcium levels at least monthly and
replace calcium as necessary. Interrupt and adjust LENVIMA as
necessary
- Across clinical studies in which 1,160 patients received
LENVIMA monotherapy, reversible posterior leukoencephalopathy
syndrome (RPLS) was reported in 4 patients. Withhold LENVIMA for
RPLS until fully resolved. Resume at reduced dose or discontinue
based on the severity and persistence of neurologic symptoms
- In DTC, hemorrhagic events occurred in 35% of patients on
LENVIMA vs 18% with placebo (2% vs 3% grade ≥3). The most
frequently reported hemorrhagic event was epistaxis (11% grade 1,
1% grade 2). Discontinuation due to hemorrhagic events occurred in
1% of patients on LENVIMA. There was 1 fatal intracranial
hemorrhage case among 16 patients who received LENVIMA and had
central nervous system metastases at baseline. In RCC, hemorrhagic
events occurred in 34% of patients on LENVIMA + everolimus vs 26%
with everolimus alone (8% vs 2% grade ≥3). The most frequently
reported hemorrhagic event was epistaxis (23% for LENVIMA +
everolimus vs 24% with everolimus alone). There was 1 fatal
cerebral hemorrhage case. Discontinuation due to hemorrhagic events
occurred in 3% of patients on LENVIMA + everolimus. Consider the
risk of severe or fatal hemorrhage associated with tumor
invasion/infiltration of major blood vessels (eg, carotid artery).
Withhold dose for grade 3 hemorrhage. Resume at reduced dose or
discontinue based on severity/persistence of hemorrhage.
Discontinue for grade 4 hemorrhage
- In DTC patients with normal baseline thyroid-stimulating
hormone (TSH), elevation of TSH level above 0.5 mU/L was observed
postbaseline in 57% of patients on LENVIMA vs 14% with placebo. In
RCC, grade 1 or 2 hypothyroidism occurred in 24% of patients on
LENVIMA + everolimus vs 2% with everolimus alone. In RCC patients
with normal or low TSH at baseline, elevation of TSH was observed
postbaseline in 60% of patients on LENVIMA + everolimus vs 3% with
everolimus alone. Monitor thyroid function prior to treatment
initiation and monthly thereafter. Treat hypothyroidism according
to standard medical practice to maintain a euthyroid state
- LENVIMA can cause fetal harm when administered to a pregnant
woman. Advise females of reproductive potential to use effective
contraception during treatment with LENVIMA and for at least 2
weeks following completion of therapy
Adverse Reactions
- In DTC, the most common adverse reactions observed in
LENVIMA-treated patients vs placebo-treated patients were
hypertension (73% vs 16%), fatigue (67% vs 35%), diarrhea (67% vs
17%), arthralgia/myalgia (62% vs 28%), decreased appetite (54% vs
18%), weight decrease (51% vs 15%), nausea (47% vs 25%), stomatitis
(41% vs 8%), headache (38% vs 11%), vomiting (36% vs 15%),
proteinuria (34% vs 3%), palmar-plantar erythrodysesthesia syndrome
(32% vs 1%), abdominal pain (31% vs 11%), and dysphonia (31% vs
5%)
- In DTC, adverse reactions led to dose reductions in 68% of
patients receiving LENVIMA and in 5% of patients receiving placebo;
18% of patients discontinued LENVIMA and 5% discontinued placebo
for adverse reactions. The most common adverse reactions (≥10%)
resulting in dose reductions of LENVIMA were hypertension (13%),
proteinuria (11%), decreased appetite (10%), and diarrhea (10%);
the most common adverse reactions (≥1%) resulting in
discontinuation of LENVIMA were hypertension (1%) and asthenia
(1%)
- In RCC, the most common adverse reactions observed in patients
treated with LENVIMA + everolimus vs everolimus alone were diarrhea
(81% vs 34%), fatigue (73% vs 40%), arthralgia/myalgia (55% vs
32%), decreased appetite (53% vs 18%), vomiting (48% vs 12%),
nausea (45% vs 16%), stomatitis/oral inflammation (44% vs 50%),
hypertension/increased blood pressure (42% vs 10%), peripheral
edema (42% vs 20%), cough (37% vs 30%), abdominal pain (37% vs 8%),
dyspnea/exertional dyspnea (35% vs 28%), rash (35% vs 40%), weight
decreased (34% vs 8%), hemorrhagic events (32% vs 26%), and
proteinuria/urine protein present (31% vs 14%)
- In RCC, adverse reactions led to dose reductions or
interruption in 89% of patients receiving
LENVIMA + everolimus and in 54% of patients receiving
everolimus. The most common adverse reactions (≥5%) resulting in
dose reductions in the LENVIMA + everolimus–treated group
were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting
(6%), nausea (5%), and proteinuria (5%). Treatment discontinuation
due to an adverse reaction occurred in 29% of patients in the
LENVIMA + everolimus–treated group and in 12% of patients
in the everolimus-treated group
Use in Specific Populations
- Because of the potential for serious adverse reactions in
nursing infants, advise women to discontinue breastfeeding during
treatment
- LENVIMA may result in reduced fertility in females of
reproductive potential and may result in damage to male
reproductive tissues, leading to reduced fertility of unknown
duration
For more information about LENVIMA, click here for the full
Prescribing Information.
About HALAVEN® (eribulin mesylate)
Injection
HALAVEN® (eribulin mesylate) is a
microtubule dynamics inhibitor indicated for the treatment of
patients with:
- Metastatic breast cancer who have previously received at least
two chemotherapeutic regimens for the treatment of metastatic
disease. Prior therapy should have included an anthracycline and a
taxane in either the adjuvant or metastatic setting.
- Unresectable or metastatic liposarcoma who have received a
prior anthracycline- containing regimen.
Discovered and developed by Eisai, eribulin is a synthetic
analog of halichondrin B, a natural product that was isolated from
the marine sponge Halichondria okadai. First in the
halichondrin class, HALAVEN is a microtubule dynamics inhibitor.
Eribulin is believed to work primarily via a tubulin-based
mechanism that causes prolonged and irreversible mitotic blockage,
ultimately leading to apoptotic cell death. Additionally, in
preclinical studies of human breast cancer, eribulin demonstrated
complex effects on the tumor biology of surviving cancer cells,
including increases in vascular perfusion resulting in reduced
tumor hypoxia, and changes in the expression of genes in tumor
specimens associated with a change in phenotype, promoting the
epithelial phenotype, opposing the mesenchymal phenotype. Eribulin
has also been shown to decrease the migration and invasiveness of
human breast cancer cells.
Important Safety Information
Warnings and Precautions
Neutropenia: Severe
neutropenia (ANC <500/mm3) lasting >1 week
occurred in 12% of patients with mBC and liposarcoma or
leiomyosarcoma. Febrile neutropenia occurred in 5% of patients with
mBC and 2 patients (0.4%) died from complications. Febrile
neutropenia occurred in 0.9% of patients with liposarcoma or
leiomyosarcoma, and fatal neutropenic sepsis occurred in 0.9% of
patients. Patients with mBC with elevated liver enzymes >3 × ULN
and bilirubin >1.5 × ULN experienced a higher incidence of Grade
4 neutropenia and febrile neutropenia than patients with normal
levels. Monitor complete blood cell counts prior to each dose, and
increase the frequency of monitoring in patients who develop Grade
3 or 4 cytopenias. Delay administration and reduce subsequent doses
in patients who experience febrile neutropenia or Grade 4
neutropenia lasting >7 days.
Peripheral Neuropathy: Grade 3 peripheral neuropathy
occurred in 8% of patients with mBC (Grade 4=0.4%) and 22%
developed a new or worsening neuropathy that had not recovered
within a median follow-up duration of 269 days (range 25-662 days).
Neuropathy lasting >1 year occurred in 5% of patients with mBC.
Grade 3 peripheral neuropathy occurred in 3.1% of patients with
liposarcoma and leiomyosarcoma receiving HALAVEN and neuropathy
lasting more than 60 days occurred in 58% (38/65) of patients who
had neuropathy at the last treatment visit. Patients should be
monitored for signs of peripheral motor and sensory neuropathy.
Withhold HALAVEN in patients who experience Grade 3 or 4 peripheral
neuropathy until resolution to Grade 2 or less.
Embryo-Fetal Toxicity: HALAVEN can cause fetal harm when
administered to a pregnant woman. Advise females of reproductive
potential to use effective contraception during treatment with
HALAVEN and for at least 2 weeks following the final dose. Advise
males with female partners of reproductive potential to use
effective contraception during treatment with HALAVEN and for 3.5
months following the final dose.
QT Prolongation: Monitor for prolonged QT intervals in
patients with congestive heart failure, bradyarrhythmias, drugs
known to prolong the QT interval, and electrolyte abnormalities.
Correct hypokalemia or hypomagnesemia prior to initiating HALAVEN
and monitor these electrolytes periodically during therapy. Avoid
in patients with congenital long QT syndrome.
Adverse Reactions
In patients with mBC receiving
HALAVEN, the most common adverse reactions (≥25%) were neutropenia
(82%), anemia (58%), asthenia/fatigue (54%), alopecia (45%),
peripheral neuropathy (35%), nausea (35%), and constipation (25%).
Febrile neutropenia (4%) and neutropenia (2%) were the most common
serious adverse reactions. The most common adverse reaction
resulting in discontinuation was peripheral neuropathy (5%).
In patients with liposarcoma and leiomyosarcoma receiving
HALAVEN, the most common adverse reactions (≥25%) reported in
patients receiving HALAVEN were fatigue (62%), nausea (41%),
alopecia (35%), constipation (32%), peripheral neuropathy (29%),
abdominal pain (29%), and pyrexia (28%). The most common (≥5%)
Grade 3-4 laboratory abnormalities reported in patients receiving
HALAVEN were neutropenia (32%), hypokalemia (5.4%), and
hypocalcemia (5%). Neutropenia (4.9%) and pyrexia (4.5%) were the
most common serious adverse reactions. The most common adverse
reactions resulting in discontinuation were fatigue and
thrombocytopenia (0.9% each).
Use in Specific Populations
Lactation: Because
of the potential for serious adverse reactions in breastfed infants
from eribulin mesylate, advise women not to breastfeed during
treatment with HALAVEN and for 2 weeks after the final dose.
Hepatic and Renal Impairment: A reduction in starting
dose is recommended for patients with mild or moderate hepatic
impairment and/or moderate or severe renal impairment.
For more information about HALAVEN, click here for the full
Prescribing Information.
About Eisai Inc.
At Eisai Inc., human health care (hhc) is our goal.
We give our first thought to patients and their families, and
helping to increase the benefits health care provides. As the U.S.
pharmaceutical subsidiary of Tokyo-based Eisai Co., Ltd., we have a
passionate commitment to patient care that is the driving force
behind our efforts to discover and develop innovative therapies to
help address unmet medical needs.
Eisai is a fully integrated pharmaceutical business that
operates in two global business groups: oncology and neurology
(dementia-related diseases and neurodegenerative diseases). Each
group functions as an end-to-end global business with discovery,
development, and marketing capabilities. Our U.S. headquarters,
commercial and clinical development organizations are located in
New Jersey; our discovery labs are
in Massachusetts and Pennsylvania; and our global demand chain
organization resides in Maryland
and North Carolina. To learn more
about Eisai Inc., please visit us at www.eisai.com/US.
Contacts:
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Media
Inquiries
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Investor
Inquiries
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Laurie
Landau
|
Ivor
Macleod
|
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Eisai Inc.
|
Eisai Inc.
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(201)
746-2510
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(201)
746-2660
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