INDIANAPOLIS, Sept. 28, 2015 /PRNewswire/ -- A Phase II
study of Eli Lilly and Company's (NYSE: LLY)
CYRAMZA® (ramucirumab) in combination with docetaxel met
its primary endpoint, demonstrating a statistically significant
increase in progression-free survival (PFS) for patients with
locally advanced or metastatic urothelial carcinoma who failed
prior platinum-based therapy. Bladder cancer accounts for the vast
majority of all urothelial carcinoma.
Final results of the Phase II trial were presented at the
European Cancer Congress (ECC2015) in Vienna, Austria (Abstract #2508) on
September 27. Based on these
findings, Lilly recently initiated a Phase III trial called RANGE,
which has begun to enroll patients.
"We are encouraged with these promising findings that could help
lead to much-needed progress in this area – people with advanced
urothelial carcinoma have limited treatment options today," said
Daniel Petrylak, M.D., professor of
medicine (medical oncology) and of urology at Yale University Cancer Center and the study's
principal investigator. "This is an aggressive type of cancer and
unfortunately, despite available first-line therapies, most
patients who have disease progression eventually succumb to their
disease. Currently, there are no agents specifically approved in
the U.S., nor is there a consistently-employed single standard of
care in the U.S. or globally, for the treatment of second-line
bladder cancer."
The three-arm trial evaluated 140 patients with advanced
carcinoma of the urothelial tract (bladder, urethra, ureter, or
renal pelvis) who, after a first-line platinum-based chemotherapy
regimen, had relapsed up to one year following the initial
treatment. Patients were randomized to receive either a combination
of ramucirumab and docetaxel (n=46), docetaxel alone (n=45), or a
combination of icrucumab and docetaxel (n=49). Treatment continued
until disease progression or toxicity levels resulted in an
interruption of treatment with one or more of the study
medicines.
Median PFS, the study's primary endpoint, was 5.4 months (HR
0.389; 95% CI: 0.389 0.235-0.643; p <0.001) on the
ramucirumab-docetaxel arm as compared to 2.8 months for patients
treated with docetaxel alone, and 1.6 months for those treated with
icrucumab and docetaxel. Objective response rate (ORR) results – or
patients who achieved either a complete response or partial
response to treatment – also favored the ramucirumab combination
arm with a significantly higher confirmed ORR (24%) compared to
those on the docetaxel arm (9%) and the icrucumab combination arm
(12%). A statistically significant benefit in disease control rate
– or patients who achieved complete response, partial response, or
stable disease – was identified on the ramucirumab arm (78%) versus
the docetaxel arm (58%) and the icrucumab arm (45%). While the
study was not powered for overall survival (OS), results favored
the ramucirumab combination arm, but were not statistically
significant, with 10.4 months median OS identified on the
ramucirumab arm compared to 9.2 months on the docetaxel arm and 6.7
months on the icrucumab arm.
The observed safety findings are consistent with prior Phase III
studies of ramucirumab and docetaxel. The most common (>5%
incidence) grade ≥3 adverse events occurring at a higher rate on
the ramucirumab-plus-docetaxel arm compared to the docetaxel arm
were fatigue (35% vs. 13%), febrile neutropenia (17% vs. 13%),
pneumonia (13% vs. 9%), anemia (13% vs. 7%), sepsis (11% vs. 7%),
edema (9% vs. 2%), diarrhea (7% vs. 2%), intestinal obstruction (7%
vs. 2%), urinary tract infection (7% vs. 2%), hypertension (7% vs.
0%), stomatitis (7% vs. 0%), and thrombocytopenia (7% vs. 0%).
The Phase III RANGE study, which is currently enrolling
patients, is a randomized, double-blind, placebo-controlled study
of ramucirumab and docetaxel versus placebo and docetaxel in
patients with locally advanced or unresectable metastatic
urothelial carcinoma whose disease progressed on or after
platinum-based chemotherapy (ClinicalTrials.gov Identifier:
NCT02426125).
"We are pleased to advance this CYRAMZA regimen into Phase III
clinical development and look forward to that trial's results,"
said Richard Gaynor, M.D., senior
vice president, product development and medical affairs for Lilly
Oncology. "Our excitement with the overall clinical development of
CYRAMZA continues to grow, with the RANGE trial in bladder cancer
marking another tumor type in late-stage evaluation in this broad
development program."
About Urothelial Carcinoma and Bladder Cancer
Urothelial carcinoma are cancers that arise in the urothelial or
transitional cells that line the urinary collecting system
including the bladder, which is the most common site for this type
of tumor. Other potential primary sites of this cancer
include the renal pelvis, ureter, and urethra.
Bladder cancer is the sixth most common and deadly cancer in the
U.S.,i with an estimated 74,000 new cases and 16,000
deaths expected in 2015.ii Globally, bladder cancer
ranks ninth in the top most common cancers overall, and the ninth
leading cause of cancer-related death, affecting approximately
430,000 people per year and resulting in more than 165,000
deaths.i
About CYRAMZA® (ramucirumab)
In the
U.S., CYRAMZA (ramucirumab) is approved for use as a single agent
or in combination with paclitaxel as a treatment for people with
advanced or metastatic gastric (stomach) or gastroesophageal
junction (GEJ) adenocarcinoma whose cancer has progressed on or
after prior fluoropyrimidine- or platinum-containing chemotherapy.
It is also approved in combination with docetaxel as a treatment
for people with metastatic non-small cell lung cancer (NSCLC) whose
cancer has progressed on or after platinum-based chemotherapy.
Additionally, it is approved with FOLFIRI as a treatment for people
with metastatic colorectal cancer (mCRC) whose cancer has
progressed on or after therapy with bevacizumab, oxaliplatin, and a
fluoropyrimidine.
There are several additional studies underway or planned to
investigate CYRAMZA as a single agent and in combination with other
anti-cancer therapies for the treatment of multiple tumor types.
This broad global development program has enrolled more than 7,000
patients across more than 50 trials of CYRAMZA
worldwide.
CYRAMZA is an antiangiogenic therapy. It is a vascular
endothelial growth factor (VEGF) Receptor 2 antagonist that
specifically binds and blocks activation of VEGF Receptor 2 by
blocking the binding of VEGF receptor ligands VEGF-A, VEGF-C, and
VEGF-D. CYRAMZA inhibited angiogenesis in an in vivo animal
model.
About Angiogenesis and VEGF Protein
Angiogenesis
is the process of making new blood vessels. In a person with
cancer, angiogenesis creates new blood vessels that give a tumor
its own blood supply, allowing it to grow and spread.
Some tumors create proteins called VEGF. These proteins attach
to the VEGF receptors of blood vessel cells causing new blood
vessels to form around the tumors, enabling growth. Blocking the
VEGF protein from linking to the blood vessels helps to inhibit
tumor growth by slowing angiogenesis and the blood supply that
feeds tumors. Of the three known VEGF receptors, VEGF Receptor 2 is
linked most closely to VEGF-induced tumor angiogenesis.
INDICATIONS
Gastric Cancer
CYRAMZA, as a
single agent or in combination with paclitaxel, is indicated for
the treatment of patients with advanced or metastatic, gastric or
gastroesophageal junction (GEJ) adenocarcinoma with disease
progression on or after prior fluoropyrimidine- or
platinum-containing chemotherapy.
Non-Small Cell Lung Cancer
CYRAMZA, in combination
with docetaxel, is indicated for the treatment of patients with
metastatic non-small cell lung cancer (NSCLC) with disease
progression on or after platinum-based chemotherapy. Patients with
epidermal growth factor receptor (EGFR) or anaplastic lymphoma
kinase (ALK) genomic tumor aberrations should have disease
progression on FDA-approved therapy for these aberrations prior to
receiving CYRAMZA.
Colorectal Cancer
CYRAMZA, in combination with
FOLFIRI (irinotecan, folinic acid, and 5-fluorouracil), is
indicated for the treatment of patients with metastatic colorectal
cancer (mCRC) with disease progression on or after prior therapy
with bevacizumab, oxaliplatin, and a fluoropyrimidine.
IMPORTANT SAFETY INFORMATION FOR CYRAMZA
WARNING:
HEMORRHAGE, GASTROINTESTINAL PERFORATION, AND IMPAIRED WOUND
HEALING
Hemorrhage:
CYRAMZA increased the risk of hemorrhage and
gastrointestinal hemorrhage, including severe and
sometimes fatal hemorrhagic events. Permanently
discontinue CYRAMZA in patients who experience severe
bleeding.
Gastrointestinal
Perforation: CYRAMZA can increase the risk of gastrointestinal
perforation, a potentially fatal event. Permanently discontinue
CYRAMZA in patients who experience a gastrointestinal
perforation.
Impaired Wound
Healing: Impaired wound healing can occur with antibodies
inhibiting the VEGF pathway. Discontinue CYRAMZA therapy in
patients with impaired wound healing. Withhold CYRAMZA prior to
surgery and discontinue CYRAMZA if a patient develops wound healing
complications.
|
Warnings and Precautions
Hemorrhage
- CYRAMZA increased the risk of hemorrhage and gastrointestinal
hemorrhage including severe and sometimes fatal hemorrhagic events.
In study 1, which evaluated CYRAMZA as a single agent in advanced
gastric cancer, the incidence of severe bleeding was 3.4% for
CYRAMZA and 2.6% for placebo. In study 2, which evaluated CYRAMZA
plus paclitaxel in advanced gastric cancer, the incidence of severe
bleeding was 4.3% for CYRAMZA plus paclitaxel and 2.4% for placebo
plus paclitaxel. Patients with gastric cancer receiving
nonsteroidal anti-inflammatory drugs (NSAIDs) were excluded from
enrollment in studies 1 and 2; therefore, the risk of gastric
hemorrhage in CYRAMZA-treated patients with gastric tumors
receiving NSAIDs is unknown. In study 3, which evaluated CYRAMZA
plus docetaxel in metastatic non-small cell lung cancer (NSCLC),
the incidence of severe bleeding was 2.4% for CYRAMZA plus
docetaxel and 2.3% for placebo plus docetaxel. Patients with NSCLC
receiving therapeutic anticoagulation or chronic therapy with
NSAIDs or other antiplatelet therapy other than once-daily aspirin
or with radiographic evidence of major airway or blood vessel
invasion or intratumor cavitation were excluded from study 3;
therefore, the risk of pulmonary hemorrhage in these groups of
patients is unknown. In study 4, which evaluated CYRAMZA plus
FOLFIRI in metastatic colorectal cancer, the incidence of severe
bleeding was 2.5% for CYRAMZA plus FOLFIRI and 1.7% for placebo
plus FOLFIRI. Permanently discontinue CYRAMZA in patients who
experience severe bleeding.
Arterial Thromboembolic Events (ATEs)
- Serious, sometimes fatal, ATEs including myocardial infarction,
cardiac arrest, cerebrovascular accident, and cerebral ischemia
occurred in clinical trials including 1.7% of 236 patients who
received CYRAMZA as a single agent for gastric cancer in study 1.
Permanently discontinue CYRAMZA in patients who experience a severe
ATE.
Hypertension
- An increased incidence of severe hypertension occurred in
patients receiving CYRAMZA as a single agent (8%) as compared to
placebo (3%), in patients receiving CYRAMZA plus paclitaxel (15%)
as compared to placebo plus paclitaxel (3%), and in patients
receiving CYRAMZA plus docetaxel (6%) as compared to placebo plus
docetaxel (2%), and in patients receiving CYRAMZA plus FOLFIRI
(11%) as compared to placebo plus FOLFIRI (3%). Control
hypertension prior to initiating treatment with CYRAMZA. Monitor
blood pressure every 2 weeks or more frequently as indicated during
treatment. Temporarily suspend CYRAMZA for severe hypertension
until medically controlled. Permanently discontinue CYRAMZA if
medically significant hypertension cannot be controlled with
antihypertensive therapy or in patients with hypertensive crisis or
hypertensive encephalopathy.
Infusion-Related Reactions (IRRs)
- Prior to the institution of premedication recommendations
across clinical trials of CYRAMZA, IRRs occurred in 6 out of 37
patients (16%), including 2 severe events. The majority of IRRs
across trials occurred during or following a first or second
CYRAMZA infusion. Symptoms of IRRs included rigors/tremors, back
pain/spasms, chest pain and/or tightness, chills, flushing,
dyspnea, wheezing, hypoxia, and paresthesia. In severe cases,
symptoms included bronchospasm, supraventricular tachycardia, and
hypotension. Monitor patients during the infusion for signs and
symptoms of IRRs in a setting with available resuscitation
equipment. Immediately and permanently discontinue CYRAMZA for
grade 3 or 4 IRRs.
Gastrointestinal Perforations
- CYRAMZA is an antiangiogenic therapy that can increase the risk
of gastrointestinal perforation, a potentially fatal event. Four of
570 patients (0.7%) who received CYRAMZA as a single agent in
advanced gastric cancer clinical trials experienced
gastrointestinal perforation. In study 2, the incidence of
gastrointestinal perforation was 1.2% for CYRAMZA plus paclitaxel
as compared to 0.3% for placebo plus paclitaxel. In study 3, the
incidence of gastrointestinal perforation was 1% for CYRAMZA plus
docetaxel as compared to 0.3% for placebo plus docetaxel. In study
4, the incidence of gastrointestinal perforation was 1.7% for
CYRAMZA plus FOLFIRI and 0.6% for placebo plus FOLFIRI. Permanently
discontinue CYRAMZA in patients who experience a gastrointestinal
perforation.
Impaired Wound Healing
- Impaired wound healing can occur with antibodies inhibiting the
VEGF pathway. CYRAMZA has not been studied in patients with serious
or nonhealing wounds. CYRAMZA, an antiangiogenic therapy, has the
potential to adversely affect wound healing. Discontinue CYRAMZA
therapy in patients with impaired wound healing. Withhold CYRAMZA
prior to surgery. Resume CYRAMZA following the surgical
intervention based on clinical judgment of adequate wound healing.
If a patient develops wound healing complications during therapy,
discontinue CYRAMZA until the wound is fully healed.
Clinical Deterioration in Child-Pugh B or C Cirrhosis
- Clinical deterioration, manifested by new onset or worsening
encephalopathy, ascites, or hepatorenal syndrome, was reported in
patients with Child-Pugh B or C cirrhosis who received single-agent
CYRAMZA. Use CYRAMZA in patients with Child-Pugh B or C cirrhosis
only if the potential benefits of treatment are judged to outweigh
the risks of clinical deterioration.
Reversible Posterior Leukoencephalopathy Syndrome
(RPLS)
- RPLS has been reported at a rate of <0.1% in clinical
studies with CYRAMZA. Confirm the diagnosis of RPLS with MRI and
discontinue CYRAMZA in patients who develop RPLS. Symptoms may
resolve or improve within days, although some patients with RPLS
can experience ongoing neurologic sequelae or death.
Proteinuria Including Nephrotic Syndrome
- In study 4, severe proteinuria occurred more frequently in
patients treated with CYRAMZA plus FOLFIRI compared to patients
receiving placebo plus FOLFIRI. Severe proteinuria was reported in
3% of patients treated with CYRAMZA plus FOLFIRI (including 3 cases
[0.6%] of nephrotic syndrome) compared to 0.2% of patients treated
with placebo plus FOLFIRI. Monitor proteinuria by urine dipstick
and/or urinary protein creatinine ratio for the development of
worsening of proteinuria during CYRAMZA therapy. Withhold CYRAMZA
for urine protein levels that are >2 g over 24 hours. Reinitiate
CYRAMZA at a reduced dose once the urine protein level returns to
<2 g over 24 hours. Permanently discontinue CYRAMZA for urine
protein levels >3 g over 24 hours or in the setting of nephrotic
syndrome.
Thyroid Dysfunction
- Monitor thyroid function during treatment with CYRAMZA. In
study 4, the incidence of hypothyroidism reported as an adverse
event was 2.6% in the CYRAMZA plus FOLFIRI-treated patients and
0.9% in the placebo plus FOLFIRI-treated patients.
Embryofetal Toxicity
- Based on its mechanism of action, CYRAMZA can cause fetal harm
when administered to pregnant women. Animal models link
angiogenesis, VEGF, and VEGF Receptor 2 (VEGFR2) to critical
aspects of female reproduction, embryofetal development, and
postnatal development. Advise pregnant women of the potential risk
to a fetus. Advise females of reproductive potential to use
effective contraception during treatment with CYRAMZA and for at
least 3 months after the last dose of CYRAMZA.
Most Common Adverse Reactions—Single Agent
- The most commonly reported adverse reactions (all grades; grade
3/4) occurring in >5% of patients receiving CYRAMZA and >2%
higher than placebo in study 1 were hypertension (16% vs 8%; 8% vs
3%), diarrhea (14% vs 9%; 1% vs 2%), headache (9% vs 3%; 0% vs 0%),
and hyponatremia (6% vs 2%; 3% vs 1%).
- The most common serious adverse events with CYRAMZA in study 1
were anemia (3.8%) and intestinal obstruction (2.1%). Red blood
cell transfusions were given to 11% of CYRAMZA-treated patients vs
8.7% of patients who received placebo.
- Clinically relevant adverse reactions reported in >1% and
<5% of CYRAMZA-treated patients vs placebo in study 1 were:
neutropenia (4.7% vs 0.9%), epistaxis (4.7% vs 0.9%), rash (4.2% vs
1.7%), intestinal obstruction (2.1% vs 0%), and arterial
thromboembolic events (1.7% vs 0%).
- Across clinical trials of CYRAMZA administered as a single
agent, clinically relevant adverse reactions (including grade
>3) reported in CYRAMZA-treated patients included proteinuria,
gastrointestinal perforation, and infusion-related reactions. In
study 1, according to laboratory assessment, 8% of CYRAMZA-treated
patients developed proteinuria vs 3% of placebo-treated patients.
Two patients discontinued CYRAMZA due to proteinuria. The rate of
gastrointestinal perforation in study 1 was 0.8% and the rate of
infusion-related reactions was 0.4%.
Most Common Adverse Reactions—Combination With
Paclitaxel
- The most commonly reported adverse reactions (all grades; grade
3/4) occurring in >5% of patients receiving CYRAMZA plus
paclitaxel and >2% higher than placebo plus paclitaxel in study
2 were fatigue/asthenia (57% vs 44%; 12% vs 6%), neutropenia (54%
vs 31%; 41% vs 19%), diarrhea (32% vs 23%; 4% vs 2%), epistaxis
(31% vs 7%; 0% vs 0%), hypertension (25% vs 6%; 15% vs 3%),
peripheral edema (25% vs 14%; 2% vs 1%), stomatitis (20% vs 7%; 1%
vs 1%), proteinuria (17% vs 6%; 1% vs 0%), thrombocytopenia (13% vs
6%; 2% vs 2%), hypoalbuminemia (11% vs 5%; 1% vs 1%), and
gastrointestinal hemorrhage events (10% vs 6%; 4% vs 2%).
- The most common serious adverse events with CYRAMZA plus
paclitaxel in study 2 were neutropenia (3.7%) and febrile
neutropenia (2.4%); 19% of patients treated with CYRAMZA plus
paclitaxel received granulocyte colony-stimulating factors.
- Adverse reactions resulting in discontinuation of any component
of the CYRAMZA plus paclitaxel combination in 2% or more patients
in study 2 were neutropenia (4%) and thrombocytopenia (3%).
- Clinically relevant adverse reactions reported in >1% and
<5% of the CYRAMZA plus paclitaxel-treated patients in study 2
were sepsis (3.1% for CYRAMZA plus paclitaxel vs 1.8% for placebo
plus paclitaxel) and gastrointestinal perforations (1.2% for
CYRAMZA plus paclitaxel vs 0.3% for placebo plus paclitaxel).
Most Common Adverse Reactions—Combination With
Docetaxel
- The most commonly reported adverse reactions (all grades; grade
3/4) occurring in >5% of patients receiving CYRAMZA plus
docetaxel and >2% higher than placebo plus docetaxel in study 3
were neutropenia (55% vs 46%; 49% vs 40%), fatigue/asthenia (55% vs
50%; 14% vs 11%), stomatitis/mucosal inflammation (37% vs 19%; 7%
vs 2%), epistaxis (19% vs 7%; <1% vs <1%), febrile
neutropenia (16% vs 10%; 16% vs 10%), peripheral edema (16% vs 9%;
0% vs <1%), thrombocytopenia (13% vs 5%; 3% vs <1%),
lacrimation increased (13% vs 5%; <1% vs 0%), and hypertension
(11% vs 5%; 6% vs 2%).
- The most common serious adverse events with CYRAMZA plus
docetaxel in study 3 were febrile neutropenia (14%), pneumonia
(6%), and neutropenia (5%). The use of granulocyte
colony-stimulating factors was 42% in CYRAMZA plus
docetaxel-treated patients versus 37% in patients who received
placebo plus docetaxel.
- In patients >65 years of age, there were 18 (8%) deaths on
treatment or within 30 days of discontinuation for CYRAMZA plus
docetaxel and 9 (4%) deaths for placebo plus docetaxel. In patients
<65 years of age, there were 13 (3%) deaths on treatment or
within 30 days of discontinuation for CYRAMZA plus docetaxel and 26
(6%) deaths for placebo plus docetaxel.
- Treatment discontinuation due to adverse reactions occurred
more frequently in CYRAMZA plus docetaxel-treated patients (9%)
than in placebo plus docetaxel-treated patients (5%). The most
common adverse events leading to treatment discontinuation of
CYRAMZA in study 3 were infusion-related reaction (0.5%) and
epistaxis (0.3%).
- For patients with nonsquamous histology, the overall incidence
of pulmonary hemorrhage was 7% and the incidence of grade >3
pulmonary hemorrhage was 1% for CYRAMZA plus docetaxel compared to
6% overall incidence and 1% for grade >3 pulmonary hemorrhage
for placebo plus docetaxel. For patients with squamous histology,
the overall incidence of pulmonary hemorrhage was 10% and the
incidence of grade >3 pulmonary hemorrhage was 2% for CYRAMZA
plus docetaxel compared to 12% overall incidence and 2% for grade
≥3 pulmonary hemorrhage for placebo plus docetaxel.
- Clinically relevant adverse reactions reported in >1% and
<5% of CYRAMZA plus docetaxel-treated patients in study 3 were
hyponatremia (4.8% CYRAMZA plus docetaxel versus 2.4% for placebo
plus docetaxel) and proteinuria (3.3% CYRAMZA plus docetaxel versus
0.8% placebo plus docetaxel).
Most Common Adverse Reactions—Combination With
FOLFIRI
- The most commonly reported adverse reactions (all grades; grade
3/4) occurring in >5% of patients receiving CYRAMZA plus FOLFIRI
and ≥2% higher than placebo plus FOLFIRI in study 4 were diarrhea
(60% vs 51%; 11% vs 10%), neutropenia (59% vs 46%; 38% vs 23%),
decreased appetite (37% vs 27%; 2% vs 2%), epistaxis (33% vs 15%;
0% vs 0%), stomatitis (31% vs 21%; 4% vs 2%), thrombocytopenia (28%
vs 14%; 3% vs <1%), hypertension (26% vs 9%; 11% vs 3%),
peripheral edema (20% vs 9%; <1% vs 0%), proteinuria (17% vs 5%;
3% vs <1%), palmar-plantar erythrodysesthesia syndrome (13% vs
5%; 1% vs <1%), gastrointestinal hemorrhage events (12% vs 7%;
2% vs 1%), hypoalbuminemia (6% vs 2%; 1% vs 0%). Twenty percent of
patients treated with CYRAMZA plus FOLFIRI received granulocyte
colony-stimulating factors.
- The most common serious adverse events with CYRAMZA plus
FOLFIRI were diarrhea (3.6%), intestinal obstruction (3.0%), and
febrile neutropenia (2.8%).
- Treatment discontinuation of any study drug due to
adverse reactions occurred more frequently in CYRAMZA plus
FOLFIRI-treated patients (29%) than in placebo plus FOLFIRI-treated
patients (13%). The most common adverse reactions leading to
discontinuation of any component of CYRAMZA plus FOLFIRI as
compared to placebo plus FOLFIRI were neutropenia (12.5% versus
5.3%) and thrombocytopenia (4.2% versus 0.8%). The most common
adverse reactions leading to treatment discontinuation of CYRAMZA
were proteinuria (1.5%) and gastrointestinal perforation
(1.7%).
- Clinically relevant adverse reactions reported in >1% and
<5% of CYRAMZA plus FOLFIRI-treated patients in study 4
consisted of gastrointestinal perforation (1.7% CYRAMZA plus
FOLFIRI versus 0.6% for placebo plus FOLFIRI).
- Thyroid-stimulating hormone (TSH) was evaluated in 224 patients
(115 CYRAMZA plus FOLFIRI-treated patients and 109 placebo plus
FOLFIRI-treated patients) with normal baseline TSH levels. Patients
received periodic TSH assessments until 30 days after the last dose
of study treatment. Increased TSH was observed in 53 (46%) patients
treated with CYRAMZA plus FOLFIRI compared with 4 (4%) patients
treated with placebo plus FOLFIRI.
Drug Interactions
- No pharmacokinetic interactions were observed between
ramucirumab and paclitaxel, between ramucirumab and docetaxel, or
between ramucirumab and irinotecan or its active metabolite,
SN-38.
Use in Specific Populations
- Pregnancy: Based on its mechanism of action, CYRAMZA can cause
fetal harm. Animal models link angiogenesis, VEGF, and VEGF
Receptor 2 (VEGFR2) to critical aspects of female reproduction,
embryofetal development, and postnatal development. There are no
available data on CYRAMZA use in pregnant women to inform any
drug-associated risks. No animal studies have been conducted to
evaluate the effect of ramucirumab on reproduction and fetal
development. Advise females of reproductive potential of the
potential risk for maintaining pregnancy, risk to the fetus, and
risk to newborn and pediatric development, and to use effective
contraception during CYRAMZA therapy and for at least 3 months
following the last dose of CYRAMZA.
- Lactation: Because of the potential risk for serious adverse
reactions in nursing infants from ramucirumab, advise women that
breastfeeding is not recommended during treatment with
CYRAMZA.
- Females of Reproductive Potential: Advise females of
reproductive potential that based on animal data CYRAMZA may impair
fertility.
Please see full Prescribing Information for
CYRAMZA, including Boxed Warnings for hemorrhage, gastrointestinal
perforation, and impaired wound healing.
RB-P HCP ISI 17SEP2015
About Lilly Oncology
For more than fifty years, Lilly
has been dedicated to delivering life-changing medicines and
support to people living with cancer and those who care for them.
Lilly is determined to build on this heritage and continue making
life better for all those affected by cancer around the world. To
learn more about Lilly's commitment to people with cancer, please
visit www.LillyOncology.com.
About Eli Lilly and Company
Lilly is a global
healthcare leader that unites caring with discovery to make life
better for people around the world. We were founded more than a
century ago by a man committed to creating high-quality medicines
that meet real needs, and today we remain true to that mission in
all our work. Across the globe, Lilly employees work to discover
and bring life-changing medicines to those who need them, improve
the understanding and management of disease, and give back to
communities through philanthropy and volunteerism. To learn more
about Lilly, please visit us at www.lilly.com and
newsroom.lilly.com/social-channels.
P-LLY
© Lilly USA, LLC 2015. ALL
RIGHTS RESERVED.
CYRAMZA is a trademark owned by or licensed to Eli Lilly and
Company, its subsidiaries, or affiliates.
This press release contains forward-looking statements (as
that term is defined in the Private Securities Litigation Reform
Act of 1995) about CYRAMZA (ramucirumab) as a potential treatment
for patients with locally advanced or metastatic urothelial
carcinoma and reflects Lilly's current belief. However, as with any
pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
Among other things, there can be no guarantee that future study
results will be consistent with the results to date or that
ramucirumab will achieve its primary study endpoints or receive
regulatory approvals. For further discussion of these and
other risks and uncertainties, see Lilly's most recent Form 10-K
and Form 10-Q filings with the United States Securities and
Exchange Commission. Except as required by law, Lilly undertakes no
duty to update forward-looking statements to reflect events after
the date of this release.
i World Health Organization. "GLOBOCAN 2012:
Estimated Cancer Incidence, Mortality and Prevalence Worldwide in
2012" http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
(Accessed September 25,
2015).
ii American Cancer Society. "What are the key
statistics about bladder cancer?"
http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics.
(Accessed September 25, 2015).
Refer To: Tracy Henrikson;
tracy.henrikson@lilly.com; (609) 240-3902 (Lilly)
Neil Hochman; n.hochman@togorun.com;
(212) 453-2067 (TogoRun)
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