INDIANAPOLIS, Oct. 16, 2017 /PRNewswire/ -- New subgroup
analysis from Eli Lilly and Company's (NYSE: LLY) Phase 3 REVEL
trial of CYRAMZA® (ramucirumab) in advanced non-small
cell lung cancer (NSCLC) was presented today at the 18th
World Conference on Lung Cancer (WCLC), hosted by the International
Association for the Study of Lung Cancer in Yokohama, Japan. Specifically, these new data
are an exploratory, post-hoc analysis focused on patients whose
cancer rapidly progressed on first-line therapy.
Time-to-progression (TTP) is defined as the time from start of
first-line therapy until progressive disease – when the person's
cancer grows, spreads or gets worse. In this analysis, aggressive
disease was defined based on rapid TTP on first-line therapy.
"Despite recent advancements, patients with aggressive, rapidly
progressing advanced non-small cell lung cancer who progress before
or at the time of their first scan – which is typically done
between nine and 12 weeks – often have a less favorable response to
their second-line therapy. This is a population that has poor
prognosis and immediate unmet needs with limited treatment
options," said Martin Reck, M.D.,
Ph.D., Department of Thoracic Oncology, Lung Clinic
Grosshansdorf.
Dr. Reck continued, "This REVEL exploratory analysis
demonstrated that efficacy, safety, and quality-of-life outcomes
among patients receiving ramucirumab plus docetaxel who have
aggressive disease with rapid progression on first-line therapy are
consistent with the outcomes of the intent-to-treat population.
These results suggest that such patients may derive meaningful
benefit from ramucirumab plus docetaxel in the second-line
setting."
The global, randomized, double-blind, placebo-controlled REVEL
Phase 3 study evaluated ramucirumab, in combination with docetaxel,
in patients with metastatic NSCLC whose cancer had progressed on or
after prior platinum-based chemotherapy for locally advanced or
metastatic disease. REVEL, which included patients with nonsquamous
and squamous forms of NSCLC, demonstrated improved overall survival
﴾OS﴿, progression‐free survival ﴾PFS﴿, and objective response rate
﴾ORR) – independent of histology.1 Please see the 'About
REVEL' section below for more detailed efficacy and safety results
in the trial's intent-to-treat (ITT) patient population. The REVEL
ITT trial results, presented at the American Society of Clinical
Oncology Annual Meeting in 2014, supported the U.S. Food and Drug
Administration approval of ramucirumab in NSCLC in December 2014.
This new subgroup analysis focused on outcomes from patients
according to their TTP on first-line treatment. Of the 1,253
patients enrolled in REVEL, on first-line therapy, 11 percent
(n=133) had TTP ≤9 weeks, 17 percent (n=209) had TTP ≤12 weeks, and
28 percent (n=354) had TTP ≤18 weeks. Baseline characteristics of
each subgroup were balanced between treatment arms.
The results show that the trend for OS and PFS outcomes favored
the ramucirumab-plus-docetaxel treatment arm, with hazard ratios
similar to those of the ITT population. In all three
subpopulations, ORR also favored the ramucirumab-plus-docetaxel
treatment arm.
|
≤9 Weeks
|
≤12 Weeks
|
≤18 Weeks
|
REVEL ITT
Population
|
|
Ramucirumab +
Docetaxel
n=71
|
Placebo +
Docetaxel
n=62
|
Ramucirumab +
Docetaxel
n=111
|
Placebo +
Docetaxel
n=98
|
Ramucirumab +
Docetaxel
n=182
|
Placebo +
Docetaxel
n=172
|
Ramucirumab +
Docetaxel
n=628
|
Placebo +
Docetaxel
n=625
|
Median OS,
months (95% CI)
|
8.28
(5.19-10.84)
|
4.83
(3.09-6.90)
|
9.10
(6.70-10.84)
|
5.78
(4.30-7.49)
|
8.51
(6.97-9.95)
|
5.95
(4.44-6.97)
|
10.51
(9.53-11.24)
|
9.13
(8.44-10.02)
|
Unstratified HR
(95% CI)
|
0.69
(0.47-1.01)
|
0.74
(0.54-1.00)
|
0.80
(0.63-1.01)
|
0.86
(0.75-0.98)
|
Median PFS,
months
(95% CI)
|
3.01
(2.66-4.07)
|
1.48
(1.41-1.87)
|
3.61
(2.76-4.21)
|
1.61
(1.45-2.60)
|
3.22
(2.79-4.14)
|
1.61
(1.48-2.60)
|
4.50
(4.21-5.36)
|
3.02
(2.79-3.94)
|
Unstratified HR
(95% CI)
|
0.69
(0.48-0.98)
|
0.73
(0.55-0.97)
|
0.72
(0.58-0.89)
|
0.78
(0.69-0.87)
|
ORR, %
(95% CI)
|
18.3
(10.1-29.3)
|
3.2
(0.4-11.2)
|
18.9
(12.1-27.5)
|
9.2
(4.3-16.7)
|
19.2
(13.8-25.7)
|
10.5
(6.3-16.0)
|
22.9
(19.7-26.4)
|
13.6
(11.0-16.5)
|
Safety overview outcomes from patients with TTP on first-line
therapy ≤18 weeks are similar to what was observed from patients
with TTP on first-line therapy ≤9 weeks and ≤12 weeks, as well as
in the ITT population. There were no new safety signals observed in
these subpopulations.
"We are encouraged by this REVEL subgroup analysis, as patients
with this aggressive type of cancer who experience rapid disease
progression on first-line therapy 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. "The results of
this REVEL analysis add to the growing body of knowledge we have
about aggressive lung cancer and demonstrates Lilly's longstanding
commitment to advancing the science in lung cancer treatment and to
improving the care of patients with this disease."
Notes to Editor
About REVEL
REVEL was a global, double-blind,
randomized Phase 3 study of CYRAMZA (ramucirumab) plus docetaxel
compared to placebo plus docetaxel in people with metastatic
non-small cell lung cancer (NSCLC) whose cancer had progressed on
or after prior platinum-based chemotherapy for locally advanced or
metastatic disease. In total, 1,253 patients – including people
with nonsquamous (73%) and squamous (26%) forms of NSCLC – were
randomized in 26 countries over six continents.1
In the trial, CYRAMZA plus docetaxel achieved a statistically
significant improvement in overall survival (the primary endpoint),
progression-free survival and objective response rate (secondary
endpoints). CYRAMZA plus docetaxel significantly extended median
overall survival compared to placebo plus docetaxel (10.5 months
[95% confidence interval (CI): 9.5, 11.2] vs. 9.1 months [95% CI:
8.4, 10.0], respectively; hazard ratio 0.86 [95% CI: 0.75, 0.98];
P=0.024). Furthermore, CYRAMZA plus docetaxel significantly
delayed disease progression (progression-free survival of 4.5
months for CYRAMZA plus docetaxel [95% CI: 4.2, 5.4] vs. 3.0 months
for placebo plus docetaxel [95% CI: 2.8, 3.9]; hazard ratio 0.76
[95% CI: 0.68, 0.86]; P<0.001). The percentage of deaths
at the time of analysis was 68% (428 patients) and 73% (456
patients) in the CYRAMZA-plus-docetaxel and placebo-plus-docetaxel
arms, respectively. The progression-free survival number of events
was 558 (89%) and 583 (93%) for CYRAMZA-plus-docetaxel and
placebo-plus-docetaxel treatment arms, respectively. Significantly
more patients responded to CYRAMZA combined with docetaxel than
with placebo plus docetaxel (23% [95% CI: 20, 26] for CYRAMZA plus
docetaxel vs. 14% [95% CI: 11, 17] for placebo plus docetaxel;
P<0.001).
The labeling for CYRAMZA contains a Boxed Warning for hemorrhage
and additional Warnings and Precautions for arterial thromboembolic
events, hypertension, infusion-related reactions, gastrointestinal
perforations, impaired wound healing, clinical deterioration in
patients with Child-Pugh B or C cirrhosis, and reversible posterior
leukoencephalopathy syndrome. In the REVEL trial, the most common
adverse reactions (all grades) observed in patients treated with
CYRAMZA plus docetaxel at a rate of ≥30% and ≥2% higher than
placebo were neutropenia (low white blood cell count) (55% vs.
46%), fatigue/asthenia (weakness) (55% vs. 50%) and
stomatitis/mucosal inflammation (37% vs. 19%). The most common
serious adverse events with CYRAMZA were febrile neutropenia (fever
and potentially other infection signs along with low white blood
cell count) (14%), pneumonia (6%), and neutropenia (5%); 42% of
patients treated with CYRAMZA plus docetaxel received granulocyte
colony-stimulating factors (treatment for low white blood cells)
vs. 37% of patients who received placebo plus docetaxel. See the
Important Safety Information at the end of this press release and
the Prescribing Information.
About Lung Cancer
Lung cancer is the leading
cause of cancer death in the U.S. and most other countries, killing
nearly 1.6 million people worldwide each year.2 In the
U.S., lung cancer is responsible for approximately 27 percent of
all cancer deaths, more than those from breast, colon and prostate
cancers combined.3 Stage IV non-small cell lung cancer
(NSCLC) is a very difficult-to-treat cancer and the prognosis is
poor for metastatic NSCLC.4 NSCLC is much more common
than other types of lung cancer, and accounts for about 85 percent
of all lung cancer cases.5 For those people affected by
NSCLC, about 70 percent have nonsquamous cell carcinoma, while
about 30 percent have squamous cell carcinoma.5
Approximately half of patients with metastatic NSCLC who begin
first-line therapy will move on to second-line
treatment.6 Despite currently available therapies, there
continues to be a need for new second-line treatment options for
patients with NSCLC.1
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. Previously completed Phase 3 studies of
ramucirumab have demonstrated benefit in advanced forms of gastric,
non-small cell lung and colorectal cancer ¾ three of the world's
leading causes of cancer-related deaths.
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
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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 Cyramza as a potential treatment for patients with
advanced non-small cell lung cancer, gastric cancer, and
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.
Among other things, there can be no guarantee that Cyramza will
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 Garon EB, et al. Ramucirumab plus docetaxel versus placebo
plus docetaxel for second-line treatment of stage IV non-small-cell
lung cancer after disease progression on platinum-based therapy
(REVEL): a multicentre, double-blind, randomised phase 3 trial.
Lancet. 2014;384:665-73.
2 International Agency for Research on Cancer. GLOBOCAN 2012. Lung
Cancer Estimated Incidence, Mortality and Prevalence Worldwide in
2012. http://globocan.iarc.fr. Accessed October 12, 2017.
3 American Cancer Society. What are the key statistics about
lung cancer?
http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-key-statistics.
Updated January 5, 2017. Accessed
October 12,
2017.
4 American Cancer
Society. Learn about cancer: Non-small cell lung cancer survival
rates by stage
http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-survival-rates.
Updated May 16, 2016. Accessed
October 12, 2017.
5 American Cancer Society. What is non-small cell lung cancer?
http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-what-is-non-small-cell-lung-cancer.
Updated May 16, 2016. Accessed
October 12,
2017.
6 Stinchcombe TE, Socinski MA. Considerations for Second-Line
Therapy of Non-Small Cell Lung Cancer. Oncologist.
2008;13:28-36.
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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content:http://www.prnewswire.com/news-releases/rapidly-progressing-advanced-non-small-cell-lung-cancer-patients-shown-to-benefit-in-new-cyramza-ramucirumab-phase-3-subgroup-analysis-300536890.html
SOURCE Eli Lilly and Company