Published: February 07, 2011
Third Phase III Study of Avastin-Based Regimen Met Primary Endpoint in Ovarian Cancer
SOUTH SAN FRANCISCO, Calif. - (BUSINESS WIRE) - Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
announced today that OCEANS, a Phase III study evaluating Avastin
(bevacizumab) in combination with chemotherapy (carboplatin and
gemcitabine) followed by continued use of Avastin alone until disease
progression in women with previously treated (recurrent),
platinum-sensitive ovarian cancer, met its primary endpoint.
The study showed that women who received a combination of Avastin and
chemotherapy, followed by the continued use of Avastin alone, lived
longer without their disease worsening (progression-free survival or
PFS), compared to women who received chemotherapy alone. No new safety
findings were observed and adverse events were consistent with those
seen in previous pivotal trials of Avastin. Full data from the OCEANS
study will be submitted for presentation at an upcoming medical meeting.
"We are very pleased with the results of the OCEANS study, as women with
ovarian cancer need new treatment options," said Hal Barron, M.D., chief
medical officer and head, Global Product Development. "Avastin has now
demonstrated a significant improvement in PFS in ovarian cancer in three
large Phase III studies, and we look forward to sharing the data at an
upcoming medical meeting."
The results from this trial build on findings from two previous Phase
III studies (GOG 0218 and ICON7) in women with newly diagnosed ovarian
cancer. Both of these studies demonstrated that front-line Avastin in
combination with standard chemotherapy (carboplatin and paclitaxel),
followed by the continued use of Avastin alone, significantly increased
the time women with ovarian cancer lived without their disease getting
worse, compared to those treated with chemotherapy alone. Roche has
submitted a European Union marketing authorization application for the
use of Avastin in the front-line setting based on the results from GOG
0218 and ICON7 and expects a decision from the Committee for Medicinal
Products for Human Use (CHMP) later this year. Genentech plans to submit
applications in the United States for the use of Avastin in ovarian
cancer in 2011.
About the OCEANS Study
OCEANS is a multicenter, randomized, double-blind, placebo-controlled
Phase III study in 484 women with platinum-sensitive recurrent
ovarian, primary peritoneal or fallopian tube cancer. Women in OCEANS
had received no more than one treatment regimen prior to enrollment in
the trial. The trial was designed to evaluate Avastin (15 mg/kg every
three weeks) in combination with carboplatin and gemcitabine
chemotherapy, followed by Avastin as a single agent until disease
progression, compared to placebo in combination with carboplatin and
gemcitabine chemotherapy followed by placebo alone. The primary endpoint
of the study was PFS. The secondary endpoints of the study included
overall survival, objective response, duration of response and safety.
The time between receiving the last dose of platinum-based chemotherapy
and disease recurrence is used to help determine the choice of
chemotherapy used in the next line of treatment. Patients are said to
have 'platinum-sensitive' disease if disease recurrence occurred more
than six months after completing their initial platinum-based
chemotherapy, and 'platinum-resistant' disease if recurrence occurred
within six months.
About Previous Phase III Studies of Avastin in Ovarian Cancer
The GOG 0218 Study
Results from the GOG 0218 study in 1,873 women with previously untreated
advanced epithelial ovarian, primary peritoneal or fallopian tube
carcinoma who already had surgery showed that women who received Avastin
(15 mg/kg) in combination with chemotherapy (paclitaxel and
carboplatin), and continued use of Avastin alone for a total duration of
15 months, had a median PFS of 14.1 months compared to 10.3 months in
women who received chemotherapy alone (hazard ratio=0.72, p<0.0001).
This is a 39 percent improvement in the likelihood of living longer
without the disease worsening, which corresponds to a 28 percent
reduction in the risk of cancer progression or death.
The GOG 0218 study protocol allowed for different ways to determine if a
patient's disease had progressed. Disease progression was measured using
both levels of a protein (CA-125) and a radiograph/scan. (CA-125 is
measured by a blood test and is sometimes used to demonstrate a response
to chemotherapy or to diagnose a recurrence or progression of ovarian
cancer.)
An analysis of efficacy was conducted for regulatory purposes that only
included disease progressions determined by radiographs/scans (excluding
progressions based on CA-125 alone). In this analysis, women who
continued Avastin, following Avastin in combination with chemotherapy,
had a median PFS of 18.2 months compared to 12.0 months in women who
received chemotherapy alone, increasing the likelihood of them living
longer without the disease worsening by 56 percent (based on a hazard
ratio=0.64, p<0.0001), which corresponds to a 36 percent reduction in
the risk of cancer progression or death.
Adverse events were consistent with those observed in pivotal trials of
Avastin.
The ICON7 Study
In a second Phase III international study in 1,528 women with previously
untreated epithelial ovarian, primary peritoneal or fallopian tube
carcinoma, women who received Avastin (7.5 mg/kg) in combination with
chemotherapy (paclitaxel and carboplatin), and continued use of Avastin
alone for a total duration of up to 12 months, had a median PFS of 18.3
months compared to 16 months in women who received chemotherapy alone
(hazard ratio=0.79, p=0.001). This is a 27 percent improvement in the
likelihood of living longer without the disease worsening which
corresponds to a 21 percent reduction in the risk of cancer progression
or death. Adverse events were consistent with those observed in pivotal
trials of Avastin.
About Ovarian Cancer
According to the American Cancer Society, in 2010 an estimated 21,880
women were diagnosed with ovarian cancer in the U.S. and approximately
13,850 died from the disease. Of the 21,880 women projected to be
diagnosed with ovarian cancer in 2010, about 80 percent, or 17,504
women, were diagnosed with an advanced stage of the disease. The disease
causes more deaths than any other gynecologic cancer and the American
Cancer Society estimates that nearly 70 percent of women with advanced
disease will die from it within five years.
Ovarian cancer is associated with high concentrations of vascular
endothelial growth factor (VEGF), a protein associated with tumor growth
and spread. Studies have shown a correlation between a high
concentration of VEGF and ascites development (excess fluid in the body
cavity), disease worsening, and a poorer prognosis in women with ovarian
cancer.
About Avastin
Avastin is a prescription-only medicine that is a solution for
intravenous infusion. It is a biologic antibody designed to specifically
bind to a protein called VEGF that plays an important role throughout
the lifecycle of the tumor to develop and maintain blood vessels, a
process known as angiogenesis. Avastin interferes with the tumor blood
supply by directly binding to the VEGF protein to prevent interactions
with receptors on blood vessel cells. Avastin does not bind to receptors
on normal or cancer cells. The tumor blood supply is thought to be
critical to a tumor's ability to grow and spread in the body
(metastasize). For more information about angiogenesis, visit http://www.gene.com.
Avastin is approved for first- and second-line treatment of metastatic
colorectal cancer (mCRC) in combination with intravenous 5-FU-based
chemotherapy, first-line treatment of unresectable, locally advanced,
recurrent or metastatic, non-squamous, non-small cell lung cancer
(NSCLC) in combination with carboplatin and paclitaxel, and metastatic
renal cell carcinoma in combination with interferon alfa.
BOXED WARNINGS and Additional Important Safety Information
People receiving Avastin may experience side effects. In clinical
trials, some people treated with Avastin experienced serious and
sometimes fatal side effects, including:
Gastrointestinal (GI) perforation: Treatment with Avastin can
result in the development of a serious side effect called GI
perforation, which is the development of a hole in the stomach, small
intestine, or large intestine. In clinical trials, this event occurred
in more people who received Avastin than in the comparison group (0.3
percent to 2.4 percent). In some cases, GI perforation resulted in
fatality. Avastin therapy should be permanently stopped if GI
perforation occurs.
Surgery and wound healing problems: Treatment with Avastin can
lead to slow or incomplete wound healing (for example, when a surgical
incision has trouble healing or staying closed). In some cases, this
event resulted in fatality. Surgery and wound healing problems occurred
more often in people who received Avastin than in the comparison group.
In a controlled clinical trial, in patients with advanced colorectal
cancer who had surgery during the course of treatment, the incidence of
wound healing complications, including serious and fatal complications,
was 15 percent for patients who received Avastin and four percent for
patients who did not receive Avastin.
Avastin therapy should not be started for at least 28 days after surgery
and until the surgical wound is fully healed. The length of time between
stopping Avastin and having voluntary surgery without the risk of wound
healing problems following surgery has not been determined. Treatment
with Avastin should be stopped at least 28 days before voluntary surgery
and in people with wound healing problems following surgery that
requires medical treatment. Treatment with Avastin should be stopped in
patients with slow or incomplete wound healing.
Severe bleeding: Treatment with Avastin can result in serious or
fatal bleeding, including coughing up blood, bleeding in the stomach,
vomiting of blood, bleeding in the brain, nosebleeds and vaginal
bleeding. These events occurred up to five times more often in people
who received Avastin compared to patients who received only
chemotherapy. Across cancer types, 1.2 percent to 4.6 percent of people
who received Avastin experienced severe to fatal bleeding. People who
have recently coughed up blood (greater than or equal to a half teaspoon
of red blood) or have serious bleeding should not receive Avastin.
Treatment with Avastin should be permanently stopped if serious bleeding
occurs.
In clinical trials for different cancer types, there were additional
serious and sometimes fatal side effects that occurred in more people
who received Avastin than in those in the comparison group. The
formation of an abnormal passage from parts of the body to another part
(non-GI fistula formation) was seen in 0.3 percent or less of people.
Severe to life-threatening stroke or heart problems were seen in 2.4
percent of people. Too much protein in the urine that led to kidney
problems was seen in less than one percent of people. Additional serious
side effects that occurred in more people who received Avastin than
those in the comparison group included severe to life-threatening high
blood pressure, which was seen in five percent to 18 percent of people,
and nervous system and vision disturbances (reversible posterior
leukoencephalopathy syndrome), which was seen in less than 0.1 percent
of people. Infusion reactions with the first dose of Avastin were
uncommon and occurred in less than three percent of people, and severe
reactions occurred in 0.2 percent of people.
Common side effects that occurred in more than 10 percent of people who
received Avastin for different cancer types, and at least twice the rate
of the comparison group, were nosebleeds, headache, high blood pressure,
inflammation of the nose, too much protein in the urine, taste change,
dry skin, rectal bleeding, tear production disorder, back pain and
inflammation of the skin (exfoliative dermatitis). Across all trials,
treatment with Avastin was permanently stopped in 8.4 percent to 21
percent of people because of side effects.
Avastin may impair fertility. Patients who are pregnant or thinking of
becoming pregnant should talk with their doctor about the potential risk
of loss of the pregnancy or the potential risk of Avastin to the fetus
during and following Avastin therapy, and the need to continue an
effective birth control method for at least six months following the
last dose of Avastin.
Women should be advised to discontinue nursing or discontinue treatment
with Avastin, taking into account the importance of Avastin to the
mother.
First-line Metastatic Colorectal Cancer
In the first-line mCRC trial, the most common severe to life-threatening
side effects that increased by two percent or more in people who
received Avastin plus IFL (chemotherapy) vs. IFL alone were weakness (10
percent vs. 7 percent), abdominal pain (8 percent vs. 5 percent), pain
(8 percent vs. 5 percent), high blood pressure (12 percent vs. 2
percent), blood clots in the veins of the body (9 percent vs. 5
percent), blood clots inside the abdomen (3 percent vs. 1 percent), a
brief loss of consciousness (3 percent vs. 1 percent), diarrhea (34
percent vs. 25 percent), constipation (4 percent vs. 2 percent), reduced
white blood cell counts (37 percent vs. 31 percent), and reduced white
blood cell counts that may increase the chance of infection (21 percent
vs. 14 percent).
Second-line Metastatic Colorectal Cancer
In the second-line mCRC trial, the most common severe to
life-threatening and fatal side effects that increased by two percent or
more in people who received Avastin plus FOLFOX4 (chemotherapy) vs.
FOLFOX4 alone were diarrhea (18 percent vs. 13 percent), nausea (12
percent vs. 5 percent), vomiting (11 percent vs. 4 percent), dehydration
(10 percent vs. 5 percent), blockage of the bowel (4 percent vs. 1
percent), numbness and tingling in fingers and toes (17 percent vs. 9
percent), nervous system disturbances (5 percent vs. 3 percent),
tiredness (19 percent vs. 13 percent), abdominal pain (8 percent vs. 5
percent), headache (3 percent vs. 0 percent), high blood pressure (9
percent vs. 2 percent), and severe bleeding (5 percent vs. 1 percent).
Non-small Cell Lung Cancer
In the NSCLC trial, the most common life-threatening to fatal side
effects that increased by two percent or more in people who received
Avastin vs. those in the comparison group were reduced white blood cell
counts (27 percent vs. 17 percent), tiredness (16 percent vs. 13
percent), high blood pressure (8 percent vs. 0.7 percent), infection
without reduced white blood cell counts (7 percent vs. 3 percent), blood
clots in the veins of the body (5 percent vs. 3 percent), fever with
reduced white blood cell counts (5 percent vs. 2 percent), inflammation
of the lungs (5 percent vs. 3 percent), infection with severe or
life-threatening reduced white blood cell counts (4 percent vs. 2
percent), low sodium levels in the blood that could lead to seizure or
coma (4 percent vs. 1 percent), headache (3 percent vs. 1 percent), and
too much protein in the urine (3 percent vs. 0 percent).
Metastatic Kidney Cancer
In the metastatic kidney cancer trial, the most common severe to fatal
side effects that increased by two percent or more in people who
received Avastin vs. those in the comparison group included tiredness
(13 percent vs. 8 percent), weakness (10 percent vs. 7 percent), too
much protein in the urine (7 percent vs. 0 percent), high blood pressure
(6 percent vs. 1 percent), and severe bleeding (3 percent vs. 0.3
percent).
For full Prescribing Information and Boxed WARNINGS on Avastin
please visit http://www.avastin.com.
About Genentech
Founded more than 30 years ago, Genentech is a leading biotechnology
company that discovers, develops, manufactures and commercializes
medicines to treat patients with serious or life-threatening medical
conditions. The company, a member of the Roche Group, has headquarters
in South San Francisco, California. For additional information about the
company, please visit http://www.gene.com.
Genentech
Krysta Pellegrino, 650-467-6800 (Media)
Sonali
Padhi, 650-467-0842 (Advocacy)
Karl Mahler, 011 41 61 687 8503
(Investor Relations)
Thomas Kudsk Larsen, 973-235-3655 (Investor
Relations)
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