INDIANAPOLIS, Sept. 10, 2017 /PRNewswire/ -- At the European
Society for Medical Oncology (ESMO) 2017 Congress today, Phase 3
RANGE data from Eli Lilly and Company (NYSE: LLY) were presented in
the Presidential Symposium (abstract#: LBA4_PR). These are the
first detailed results from the global, randomized, double-blinded,
placebo-controlled RANGE study of CYRAMZA®
(ramucirumab), in combination with docetaxel, in patients with
advanced or metastatic urothelial carcinoma whose disease
progressed on or after platinum-based chemotherapy. The data showed
a statistically significant improvement in progression-free
survival (PFS) in patients treated with ramucirumab plus docetaxel
when compared to those who received placebo plus docetaxel, with a
46 percent prolongation in median PFS. These RANGE data will be
published online in The Lancet on Tuesday, September 12, 2017 at 6:30 p.m. EDT.
RANGE is the first and only Phase 3 study of any therapy to show
superior PFS over chemotherapy in a post-platinum setting in
urothelial cancer. Also, ramucirumab is the first anti-angiogenic
agent to extend PFS in a Phase 3 trial in urothelial cancer.
Patients previously treated with a checkpoint inhibitor were
allowed to enroll in the RANGE study. PFS is the trial's primary
endpoint, and secondary endpoints include overall survival (OS),
objective response rate (ORR), disease control rate (DCR) and
patient-reported outcomes (PRO).
"It's been an exciting and eventful time in urothelial carcinoma
medicine research and development over the last several years,
going from very few approved therapies to many new treatment
options now available this year. However, many patients treated
with these new therapies have progressive disease as best
response--meaning that their cancer is still growing, spreading or
getting worse. This is what is driving the clinical community to
continue to investigate additional targets for treatments that can
help quickly control disease progression," said Daniel Petrylak, M.D., professor of medical
oncology and urology at Yale Cancer Center and principal
investigator of the RANGE study. "We are looking at ramucirumab in
this way, as RANGE is the first Phase 3 study to show the benefit
of targeting angiogenesis in urothelial cancer and the first
therapy to show superior progression-free survival over
chemotherapy in a post-platinum setting. This benefit also confirms
the efficacy seen in the Phase 2 study."
Patients treated on the ramucirumab-plus-docetaxel arm (n=263)
achieved a median PFS of 4.1 months compared to 2.8 months for
patients on the placebo-plus-docetaxel arm (n=267). The PFS hazard
ratio (HR) was 0.757 (95% CI, 0.607-0.943, p=0.0118), which
corresponds to a 24 percent reduction in the rate of disease
progression or death. These investigator-assessed PFS results were
confirmed by a blinded central radiographic review (HR, 0.672; 95%
CI, 0.536-0.842; p=0.0005). In addition, PFS results were
consistent across pre-specified subgroups.
Importantly, the PFS HR was consistent across three subgroups
defined by poor prognostic factors (HR, 0.694-0.764)--patients with
ECOG 1 performance status, liver metastases or a short interval of
<3 months since prior therapy. The majority of patients (415 of
530) had at least one risk factor--44 percent had two or more.
An analysis of the PFS data in the first 437 patients of the
intent-to-treat (ITT) population showed that the
ramucirumab-plus-docetaxel arm had an ORR of 24.5 percent (95% CI,
18.8-30.3) compared to 14.0 percent in the placebo-plus-docetaxel
arm (95% CI, 9.4-18.6). Given the gated statistical design of the
protocol, statistical analysis for significance of ORR will be
assessed following the OS endpoint (at the time of the primary PFS
analysis, OS data were immature). Although the number of enrolled
patients that had received a prior immune checkpoint inhibitor was
relatively small--as this trial was initiated in 2015 when several
other such trials were ongoing and no approved agents were
available--the ORR at this PFS readout in those patients was
consistent with the ITT population. Disease control in the ITT
population occurred in 63.4 percent (95% CI, 57.0-69.8) of patients
in the ramucirumab-plus-docetaxel arm and 56.1 percent (95% CI,
49.6-62.7) in the placebo-plus-docetaxel arm.
The PFS and ORR demonstrated at this RANGE data readout confirm
previously reported results from a Phase 2 study evaluating the
combination of ramucirumab and docetaxel in the same patient
population.1
The safety profile observed in the RANGE study at this data
readout was consistent with what has previously been observed for
ramucirumab. Grade ≥3 adverse events were reported at a
similar frequency in both arms. The grade ≥3 adverse events
occurring at a rate of five percent or greater, and that were
higher on the ramucirumab-plus-docetaxel arm compared to the
placebo-plus-docetaxel arm, were neutropenia (15.1% vs.
13.6%), febrile neutropenia (9.7% vs. 6.4%), and hypertension (5.8%
vs. 1.9%). Grade ≥3 cardiovascular events, including arterial or
venous thromboembolism and congestive heart failure, were rare in
both arms, affecting ≤ 2% of patients.
"We are encouraged by these results from the RANGE study, as
patients with this aggressive type of cancer who experience disease
progression urgently need additional treatment options that can
help stop or slow the cancer from growing and spreading," said
Levi Garraway, M.D., Ph.D., senior
vice president, global development and medical affairs, Lilly
Oncology. "These RANGE data provide additional evidence in favor of
combining CYRAMZA with other therapeutic backbones, which has now
demonstrated an efficacy improvement in treating several types of
aggressive metastatic cancers."
RANGE OS data are immature and final OS results are currently
expected in mid-2018. Investigators, patients and Lilly study
personnel involved in patient-level decision-making will remain
blinded to patient-treatment assignments until that time.
Overall, RANGE is the sixth positive Phase 3 trial of
ramucirumab to date. Previously completed Phase 3 studies of
ramucirumab have demonstrated benefit in advanced forms of gastric,
non-small cell lung and colorectal cancer--three of the world's
leading causes of cancer-related deaths.
Notes to Editor
About the RANGE Study
The RANGE trial, which enrolled
530 patients globally, is a randomized, double-blind study designed
to evaluate the safety and efficacy of ramucirumab and docetaxel
versus placebo and docetaxel in patients with locally advanced or
unresectable or metastatic urothelial carcinoma whose disease
progressed on or after platinum-based chemotherapy. The trial
includes: 1) patients who progressed following adjuvant and/or
neoadjuvant therapy; 2) patients who progressed following
first-line metastatic therapy; and 3) patients who had received
prior platinum-based and immune checkpoint inhibitor regimens. The
trial's primary endpoint is progression-free survival, and other
secondary endpoints include overall survival, objective response
rate, disease control rate and patient-reported outcomes.
About Urothelial Cancer
Urothelial cancer includes carcinomas 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 accounts for the
majority of all urothelial carcinoma.
Worldwide, bladder cancer ranks ninth in the topmost common
cancers overall,2 and the ninth leading cause of
cancer-related deaths, afflicting approximately 430,000 people per
year and resulting in more than 165,000 deaths.3 The
global incidence of bladder cancer increased 11 percent from 2008
to 2012. In the U.S.,
bladder cancer is the sixth most common and deadly
cancer,4 with an estimated 79,000 new cases and nearly
17,000 deaths expected in 2017.5
Generally, this is an aggressive disease and, unfortunately,
despite recently approved therapies, the majority of patients who
have disease progression will eventually succumb to their
cancer.
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.
Ramucirumab is being investigated in a broad global development
program that has enrolled more than 10,000 patients across more
than 70 trials worldwide. There are several studies underway or
planned to investigate ramucirumab as a single agent and in
combination with other anti-cancer therapies for the treatment of
multiple tumor types.
Ramucirumab 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. Ramucirumab 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
- 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. 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. 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. 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%). 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. 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
- 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
- CYRAMZA has not been studied in patients with serious or
nonhealing wounds. CYRAMZA 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.
Reversible Posterior Leukoencephalopathy Syndrome
(RPLS)
- RPLS has been reported at a rate of <0.1% in clinical
studies with CYRAMZA. 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.
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 Warning for hemorrhage, gastrointestinal
perforation, and impaired wound healing.
RB-P-HCP ISI
16FEB2017
About Lilly Oncology
For more than 50 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 2017. ALL
RIGHTS RESERVED.
CYRAMZA is a trademark owned by or licensed to Eli Lilly and
Company, its subsidiaries, or affiliates.
Lilly Forward-Looking Statement
This press release
contains forward-looking statements (as that term is defined in the
Private Securities Litigation Reform Act of 1995) about ramucirumab
as a potential treatment for patients with locally advanced or
unresectable or metastatic urothelial carcinoma, 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. Among other things,
there can be no guarantee that ramucirumab will achieve its primary
study endpoints, receive additional regulatory approvals or be
commercially successful. 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.
1 Petrylak DP, Tagawa ST, Kohli M,, et al. Docetaxel
as Monotherapy or Combined With Ramucirumab or Icrucumab in
Second-Line Treatment for Locally Advanced or Metastatic Urothelial
Carcinoma: An Open-Label, Three-Arm, Randomized Controlled Phase II
Trial. J Clin Oncol. 2016; 34(13):1500-9.
2 World Cancer Research Fund International. "Bladder
cancer statistics." Accessed September 7,
2017. Available at:
http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/bladder-cancer-statistics.
3 World Health Organization. "GLOBOCAN 2012: Estimated
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Accessed September 7, 2017. Available
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4 National Institute of Health National Cancer Institute
Surveillance, Epidemiology, and End Results Program. "Cancer Stat
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https://seer.cancer.gov/statfacts/html/urinb.html.
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Refer
to:
Tracy Henrikson;
tracy.henrikson@lilly.com; 609-240-3902 (media)
Phil
Johnson; johnson_philip_l@lilly.com; 317-655-6874
(investors)
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