INDIANAPOLIS, April 24, 2015 /PRNewswire/ -- Eli Lilly and
Company (NYSE: LLY) has received its fourth U.S. Food and Drug
Administration (FDA) approval for CYRAMZA®
(ramucirumab). CYRAMZA (ramucirumab injection 10 mg/mL solution) is
now also indicated in combination with FOLFIRI (irinotecan, folinic
acid, and 5-fluorouracil) chemotherapy for the treatment of
patients with metastatic colorectal cancer (mCRC) with disease
progression on or after prior therapy with bevacizumab,
oxaliplatin, and a fluoropyrimidine.
"CYRAMZA now has approvals in advanced or metastatic forms of
three of the world's most common and deadly cancers – gastric,
non-small cell lung, and colorectal – with four FDA approvals
received in just over a year," said Sue Mahony, Ph.D., senior
vice president and president, Lilly Oncology. "This progress is
encouraging and supports our ongoing development program for
CYRAMZA. Achieving today's milestone is another example of Lilly's
commitment to people living with gastrointestinal cancers."
Dr. Mahony added, "We are also pleased with the efficient and
collaborative reviews we had with the FDA on these submissions."
While granted a standard review, this application for CYRAMZA in
mCRC was reviewed and approved in approximately nine weeks
following its submission to the FDA. All three supplemental
applications for CYRAMZA received FDA approval within six months
from the time of submission.
The approval is based on the Phase III trial known as RAISE,
which compared CYRAMZA plus FOLFIRI to placebo plus FOLFIRI in
people with mCRC who had disease progression on or after prior
therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine.
Efficacy endpoints in the trial included the major efficacy outcome
measure of overall survival (OS) and the supportive efficacy
outcome measure of progression-free survival (PFS). The labeling
for CYRAMZA contains Boxed Warnings for:
hemorrhage, including severe and sometimes fatal events;
gastrointestinal (GI) perforation, a potentially fatal
event; and impaired wound healing. CYRAMZA should be
permanently discontinued in patients who experience severe bleeding
or a GI perforation. CYRAMZA should be withheld prior to surgery
and discontinued if a patient develops wound healing complications.
See the Important Safety Information at the end of this press
release and the Prescribing Information.
For patients receiving CYRAMZA treatment, Lilly is committed to
offering patient assistance programs. Patients, physicians,
pharmacists, or other healthcare professionals with additional
questions about CYRAMZA should contact The Lilly Answers Center at
1-800-LillyRx (1-800-545-5979) or visit www.lilly.com.
Healthcare professionals may also find additional product
information on CYRAMZA at www.CYRAMZA.com.
About CYRAMZA® (ramucirumab)
In the
U.S., CYRAMZA (ramucirumab) is approved for use as a single agent
or in combination with paclitaxel (a type of chemotherapy) 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 (a type of chemotherapy) 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 (a type of chemotherapy)
as a therapy for people with metastatic colorectal cancer (mCRC)
whose cancer has progressed on or after therapy with bevacizumab,
oxaliplatin, and a fluoropyrimidine.
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
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 and 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.
About the RAISE Trial
RAISE was a global, double-blind
Phase III study of CYRAMZA plus FOLFIRI compared to placebo plus
FOLFIRI as a second-line treatment for mCRC in patients who had
disease progression on or after prior therapy with bevacizumab,
oxaliplatin, and a fluoropyrimidine. Patients were randomized in a
1:1 ratio to receive CYRAMZA plus FOLFIRI (n=536) or placebo plus
FOLFIRI (n=536) every two weeks.
In the RAISE trial, patients treated with the CYRAMZA-FOLFIRI
combination achieved a median OS, the study's primary endpoint, of
13.3 months as compared to those treated with placebo-FOLFIRI who
achieved 11.7 months, a statistically significant improvement that
reduced the risk of patient death by 15 percent (HR 0.85; 95%
CI: 0.73-0.98; p=0.023). The percentage of deaths at the time of
analysis was 69 percent (372 patients) and 74
percent (397 patients) in the CYRAMZA-plus-FOLFIRI and
placebo-plus-FOLFIRI treatment arms, respectively. The CYRAMZA
combination also demonstrated a statistically significant
improvement in the secondary endpoint of PFS over the
placebo-FOLFIRI regimen, with a median PFS of 5.7 months vs. 4.5
months, respectively (HR 0.79; 95% CI: 0.70-0.90; p<0.001). The
percentage of events at the time of analysis was 89
percent (476 patients) and 92 percent (494 patients) in
the CYRAMZA-plus-FOLFIRI and placebo-plus-FOLFIRI treatment arms,
respectively. In the RAISE trial, randomization was stratified by
geographic region, tumor KRAS status, and time to disease
progression after beginning first-line treatment (<6 months vs.
≥6 months). The treatment effect was consistent across the
pre-specified stratification factors.
The labeling for CYRAMZA contains Boxed Warnings for hemorrhage,
GI perforation, and impaired wound healing and additional Warnings
and Precautions for arterial thromboembolic events, hypertension,
infusion-related reactions, clinical deterioration in patients with
Child-Pugh B or C cirrhosis, reversible posterior
leukoencephalopathy syndrome, proteinuria including nephrotic
syndrome, thyroid dysfunction, and embryofetal toxicity. The most
common adverse reactions (all grades) observed in
CYRAMZA-plus-FOLFIRI-treated patients at a rate of ≥30
percent and ≥2 percent higher than placebo plus FOLFIRI
were diarrhea (60% vs. 51%), neutropenia (59% vs. 46%), decreased
appetite (37% vs. 27%), epistaxis (33% vs. 15%), and stomatitis
(31% vs. 21%). The most common serious adverse events with CYRAMZA
plus FOLFIRI were diarrhea (3.6%), intestinal obstruction (3.0%),
and febrile neutropenia (2.8%). See the Important Safety
Information at the end of this press release and the Prescribing
Information.
About Colorectal Cancer
Colorectal cancer (CRC) is a
cancer that develops in the colon or the rectum, which are both
parts of the gastrointestinal system. Metastatic CRC (mCRC) occurs
when the disease has spread to at least one distant organ, such as
the liver, lungs, or lining of the abdomen.
Despite advances in treating CRC in recent years, the mortality
rate remains significant. CRC is the second leading cause of cancer
death in the U.S. and fourth leading cause of cancer death
worldwide, killing nearly 700,000 people in
2012.i,ii,iii
The global incidence of CRC is estimated to be over 1.3
million.i Approximately one out of five CRC patients is diagnosed with metastatic
disease, and the five-year survival rate for these patients is 12.9
percent.iii
Lilly PatientOne
The Lilly PatientOne program
addresses financial and coverage issues for qualified uninsured,
underinsured, and insured patients who are prescribed a Lilly
Oncology product. Lilly PatientOne provides reimbursement
assistance for eligible patients who are prescribed a Lilly
Oncology product, such as information about coding and billing,
prior authorization, benefits investigation, and denied claim
appeals, as well as operating a patient assistance program. To
learn more, visit www.LillyPatientOne.com or call 1-866-4PatOne
(1-866-472-8663).
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. 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%), and stomatitis (31% vs 21%; 4% vs 2%). 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
24APR2015
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)
RB96717 04/2015 © 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 about the potential of CYRAMZA
(ramucirumab) as a treatment of metastatic colorectal cancer and
reflects Lilly's current beliefs. However, as with any
pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
There can be no guarantee that future study results and patient
experience will be consistent with the study findings to date.
There can also be no guarantee that CYRAMZA will receive regulatory
approval for any future indications or that it will prove to be
commercially successful. For further discussion of these and other
risks and uncertainties that could cause actual results to differ
from Lilly's expectations, please see the company's latest Forms
10-K and 10-Q filed with the U.S. Securities and Exchange
Commission. Except as required by law, Lilly undertakes no duty to
update forward-looking statements.
|
i Globocan: Estimated Cancer Incidence,
Mortality and Prevalence Worldwide, 2012.
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx (Accessed:
April 22, 2015).
ii American Cancer Society, Cancer Facts
& Figures 2015. Atlanta:
American Cancer Society; 2015.
http://www.cancer.org/acs/groups/content/@editorial/documents/document/acspc-044552.pdf (Accessed:
March 5, 2015).
iii National Cancer Institute, SEER 18
2004-2010, All Races, Both Sexes by SEER Summary Stage 2000.
http://seer.cancer.gov/statfacts/html/colorect.html (Accessed:
April 22, 2015).
Refer To:
Tracy Henrikson;
tracy.henrikson@lilly.com; (609) 240-3902 (Lilly Oncology)
Mariann Caprino;
m.caprino@togorun.com; (917) 242-1087 (TogoRun)
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visit:http://www.prnewswire.com/news-releases/lillys-cyramza-ramucirumab-receives-fourth-fda-approval-300071988.html
SOURCE Eli Lilly and Company