Genentech Study Showed That Avastin Helped People with Newly Diagnosed
Glioblastoma Live Longer without Their Disease Worsening When Added to
Radiation and Chemotherapy
WASHINGTON -- November 17, 2012
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today
announced results from the positive Phase III AVAglio study. The study showed
Avastin^® (bevacizumab) in combination with radiation and temozolomide
chemotherapy reduced the risk of cancer worsening or death (progression-free
survival; PFS) by 36 percent compared to radiation and temozolomide
chemotherapy plus placebo (HR=0.64; p<0.0001) in people with newly diagnosed
glioblastoma, the most common and aggressive form of primary brain cancer. PFS
assessed by trial investigators was a co-primary endpoint for the study. The
interim results for overall survival (OS), the other co-primary endpoint, did
not reach statistical significance (HR=0.89; p=0.2135). Final data on OS are
expected in 2013. The data were presented today at the 17^th Annual Meeting of
the Society for Neuro-Oncology in Washington, D.C.
No new safety findings were observed in the AVAglio study and adverse events
were consistent with those seen in previous trials of Avastin across tumor
types for approved indications. Adverse events of special interest (all
Grades) that occurred more often in the Avastin arm compared to the radiation
and chemotherapy arm (>2 percent increased incidence) were bleeding in
mucous/skin linings (26.7 percent vs. 8.9 percent) or other regions of the
body excluding the brain (11.6 percent vs. 8.1 percent), high blood pressure
(37.5 percent vs. 13 percent), too much protein in the urine (proteinuria; 14
percent vs. 4 percent) and blood clots (arterial thromboembolic; 5.0 percent
vs. 1.6 percent).
Avastin is currently approved in the United States under the U.S. Food and
Drug Administration’s (FDA) accelerated approval program for the treatment of
adults with glioblastoma who have progressive disease following prior therapy.
In glioblastoma, it is approved for use as a single therapy and not in
combination with other therapies. The effectiveness of Avastin is based on
improvement in objective response rate. Currently, no data are available from
randomized controlled trials demonstrating improvement in disease-related
symptoms or increased survival with Avastin in glioblastoma.
“People with newly diagnosed glioblastoma have few treatment options and need
new medicines,” said Hal Barron M.D., chief medical officer and head of Global
Product Development. “An important outcome from the AVAglio study was that
patients who received Avastin plus radiation and chemotherapy lived
significantly longer without their disease getting worse, and we plan to
discuss these data with regulatory authorities.”
The results of the Phase III AVAglio trial were presented in Plenary Session 5
by Professor Olivier Chinot, AVAglio principal investigator, President of
Association des Neuro-Oncologue d'Expression Française (ANOEF), and head of
the neuro-oncology department, University Hospital Timone, Marseille, France
(Abstract OT-03, Saturday, November 17, 10:45 a.m. Eastern Time).
AVAglio Study Results
*The 36 percent reduction in the risk of disease worsening or death can
also be referred to as a 56 percent improvement in PFS (HR=0.64;
*A 4.4 month improvement in median PFS was observed when people with newly
diagnosed glioblastoma received Avastin in combination with radiation and
chemotherapy compared to those who received radiation and chemotherapy
plus placebo (10.6 months vs. 6.2 months, respectively).
*Interim results for OS did not reach statistical significance (HR=0.89;
p=0.2135). Final data on OS are expected in 2013.
*An independent review committee assessment of PFS showed a 39 percent
reduction in the risk of disease worsening or death, which can also be
referred to as a 64 percent improvement in PFS (HR=0.61; p<0.0001). This
was consistent with the magnitude of benefit assessed by the trial
*The one-year survival rate was 66 percent for the placebo arm versus 72
percent in the Avastin arm (p=0.052).
*Adverse events (Grade 3-5) of special interest occurred in 28.7 percent of
patients in the Avastin arm compared to 15.2 percent of patients in the
radiation and chemotherapy plus placebo arm. Adverse events (Grade 3-5) of
special interest that occurred more often (>2 percent increased incidence)
in the Avastin arm compared to the control arm were high blood pressure
(10.3 percent vs. 2.0 percent) and too much protein in the urine
(proteinuria; 3.7 percent vs. 0 percent).
About the AVAglio Study
AVAglio is a Phase III, randomized, double-blind, placebo controlled trial
that assessed the efficacy and safety profile of Avastin in combination with
radiation and temozolomide chemotherapy following surgery or biopsy in
patients with newly diagnosed glioblastoma. Patients were randomized to
*Avastin plus radiation and temozolomide chemotherapy for six weeks
followed by a four-week break. Patients then received Avastin and
temozolomide for up to six cycles, followed by Avastin alone until disease
*Radiation, temozolomide and placebo for six weeks followed by a four-week
break. Patients then received temozolomide and placebo for up to six
cycles, followed by placebo until disease progression.
The co-primary endpoints of the study were OS and PFS as assessed by trial
investigators. Secondary endpoints included PFS as assessed by an independent
review committee, one- and two-year survival rates, health-related quality of
life measures, and safety profile.
By meeting its co-primary endpoint of PFS, AVAglio is the first positive Phase
III study in newly diagnosed glioblastoma since 2005.
Glioma (cancer of the glial cells) is the most common type of malignant
primary brain tumor (a tumor that originates in the brain), accounting for
approximately one-third of all cases diagnosed. Glioblastoma (or glioblastoma
multiforme) is the most common and the most aggressive type of glioma,
affecting approximately 10,000 people per year in the United States.
Glioblastoma tumors have among the highest levels of vascular endothelial
growth factor (VEGF) of any solid tumor.
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 is designed to interfere with the tumor blood supply by directly
binding to the VEGF protein to prevent interactions with receptors on blood
vessel 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.
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
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 (2.4 percent to 0.3 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 metastatic 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 require medical treatment.
Treatment with Avastin should be stopped in patients with slow or incomplete
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
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 2.6 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. Avastin can cause fertility issues for women.
Avastin could cause a woman’s ovaries to stop working and may impair her
ability to have children.
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
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.
In the glioblastoma clinical trial AVF3708g, the most common side effects in
people who received Avastin alone were infection (occurred in 55 percent of
people), tiredness (occurred in 45 percent of people), headache (occurred in
37 percent of people), high blood pressure (occurred in 30 percent of people),
nosebleeds (occurred in 19 percent of people), and diarrhea (occurred in 21
percent of people). Some of these common side effects were severe to
life-threatening or fatal: infection (occurred in 10 percent of people),
tiredness (occurred in 4 percent of people), headache (occurred in 4 percent
of people), high blood pressure (occurred in 8 percent of people), and
diarrhea (occurred in 1 percent of people). Two fatalities were possibly
related to Avastin: one from bleeding in the abdomen, and one from severely
reduced white blood cell counts that led to infection.
People who received Avastin alone or Avastin plus irinotecan* (chemotherapy)
experienced mild to life-threatening side effects including bleeding (occurred
in 40 percent of people), nosebleeds (occurred in 26 percent of people),
bleeding in the brain (occurred in 5 percent of people), high blood pressure
(occurred in 32 percent of people), blood clots in the veins of the body
(occurred in 8 percent of people), stroke or heart problems (occurred in 6
percent of people), surgery and wound healing problems (occurred in 6 percent
of people), too much protein in the urine (occurred in 4 percent of people),
the development of a hole in the stomach, small intestine or large intestine
(occurred in 2 percent of people), and nervous system and vision disturbances
(occurred in 1 percent of people). People who received Avastin alone or
Avastin plus irinotecan (chemotherapy) experienced severe to fatal side
effects including bleeding (occurred in 2 percent of people), bleeding in the
brain (occurred in 1 percent of people), high blood pressure (occurred in 5
percent of people), blood clots in the veins of the body (occurred in 7
percent of people), stroke or heart problems (occurred in 3 percent of
people), surgery and wound healing problems (occurred in 3 percent of people),
too much protein in the urine (occurred in 1 percent of people), and the
development of a hole in the stomach, small intestine or large intestine
(occurred in 2 percent of people). Bleeding within the brain occurred in eight
of 163 people; two people had severe to life threatening bleeding.
* Avastin is not approved for use for glioblastoma in combination with
For full Prescribing Information and Boxed WARNINGS on Avastin, please visit
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
Holli Dickson, 650-922-1269
Jen Mills, 415-971-2409
Thomas Kudsk Larsen, 650-467-2016
Karl Mahler, 011 41 61 687 8503
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