|[January 23, 2013]
FDA Approves New Use of Avastin Plus Chemotherapy for People with Metastatic Colorectal Cancer
SOUTH SAN FRANCISCO, Calif. --(Business Wire)--
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),
today announced that the U.S. Food and Drug Administration (FDA) has
approved a new use of Avastin® (bevacizumab) in combination
with fluoropyrimidine-based irinotecan or oxaliplatin chemotherapy for
people with metastatic colorectal cancer (mCRC). The new indication will
allow people who received Avastin plus an irinotecan or oxaliplatin
containing chemotherapy as an initial treatment (first-line) for mCRC to
continue to receive Avastin plus a different irinotecan or oxaliplatin
containing chemotherapy after their cancer worsens (second-line
"The majority of people diagnosed with metastatic colorectal cancer
receive Avastin plus chemotherapy as their initial treatment," said Hal
Barron, M.D., chief medical officer and head of Global Product
Development. "These people now have the option to continue with Avastin
plus a new chemotherapy after their cancer worsens, which may help them
live longer than changing to the new chemotherapy alone."
Avastin in combination with fluoropyrimidine-irinotecan or
fluoropyrimidine-oxaliplatin based chemotherapy is now indicated for the
second-line treatment of patients with metastatic colorectal cancer who
have progressed on a first-line Avastin containing regimen. The approval
is based on positive results from the Phase III ML18147 study, which
were presented at the 2012 American Society of Clinical Oncology annual
meeting and showed that people who continued to receive an Avastin-based
regimen after their cancer worsened lived longer than people who
switched to chemotherapy alone.
The risk of death was reduced by 19 percent for people who received
Avastin in combination with standard chemotherapy in both the first-
and second-line compared to those who received chemotherapy alone
(HR=0.81, p=0.0057). Median overall survival was 11.2 months compared
to 9.8 months.
The risk of the cancer worsening or death (progression-free survival;
PFS) was reduced by 32 percent (HR=0.68, p<0.0001). Median PFS was 5.7
months compared to 4.1 months.
Overall survival and PFS were calculated from the time patients were
randomized to the second-line treatment.
There was no significant difference in response rate between treatment
Adverse events (AEs) in ML18147 were consistent with those seen in
previous pivotal trials of Avastin in mCRC.
Avastin is the only biologic medicine approved by the FDA to treat
people with mCRC in combination with intravenous 5FU-based chemotherapy
as an initial treatment, as treatment for people whose cancer worsened
after chemotherapy alone, and now as a treatment for people whose cancer
has worsened after initial treatment with an Avastin-based regimen. This
is the third approval for Avastin in mCRC based on improved overall
survival. Avastin is not indicated for adjuvant treatment of colon
Avastin is approved in Europe in combination with fluoropyrimidine-based
chemotherapy for the treatment of adult patients with metastatic
carcinoma of the colon or rectum. The European product information has
been updated based on the positive results of the Phase III ML18147
study with an implementation date of December 12, 2012, allowing people
with mCRC who received Avastin plus chemotherapy as a first-line
treatment to continue to receive Avastin plus chemotherapy after their
cancer worsens as part of their second-line treatment.
About the ML18147 Study
ML18147 was a randomized, open-label, Phase III multicenter,
multinational trial evaluating the efficacy and safety profile of
Avastin plus standard second-line chemotherapy in 820 patients with mCRC
whose disease had progressed following Avastin plus standard first-line
chemotherapy (irinotecan or oxaliplatin-based). Patients were randomized
at progression to one of two treatment arms:
Arm A: Chemotherapy* plus Avastin (equivalent of 2.5 mg/kg i.v. per
Arm B: Chemotherapy* alone
*Depending on the first-line chemotherapy backbone
(fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based), the
chemotherapy backbone was switched in the second-line setting.
The primary endpoint of the study was overall survival measured from the
time patients were randomized to the second-line treatment. The
secondary efficacy endpoints of the study included PFS, overall response
rate and safety profile.
About Colorectal Cancer
According to the American Cancer Society, colorectal cancer is the third
most commonly diagnosed cancer in both men and women in the United
States and the third leading cause of cancer deaths. In 2012, more than
143,000 people were diagnosed and nearly 52,000 individuals were
projected to die from the disease in the United States. If colorectal
cancer spreads (metastasizes) to distant organs, such as the lungs or
the liver, five-year survival declines to 12 percent.
About Genntech Access Solutions
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Genentech Access Solutions is a team of more than 350 Genentech
employees who help those who need our medicines. Our knowledgeable and
experienced specialists can help patients and medical practices navigate
the access and reimbursement process and provide assistance to eligible
patients in the United States who do not have insurance coverage or who
cannot afford their out-of-pocket co-pay costs. For more information,
please visit http://www.Genentech-Access.com.
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 vascular endothelial growth factor (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).
Avastin Indications in Metastatic Colorectal Cancer:
Avastin is indicated for the first- or second-line treatment of
patients with metastatic carcinoma of the colon or rectum in
combination with intravenous 5-fluorouracil-based chemotherapy.
Avastin in combination with fluoropyrimidine-irinotecan or
fluoropyrimidine-oxaliplatin based chemotherapy is indicated for the
second-line treatment of patients with metastatic colorectal cancer
who have progressed on a first-line Avastin containing regimen.
Avastin is not indicated for adjuvant treatment of colon cancer.
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 (2.4
percent to 0.3 percent). In some cases, GI perforation resulted in
fatality. Avastin therapy should be permanently stopped if GI
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 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
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 effects.
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
First-line Metastatic Colorectal Cancer
In the first-line metastatic colorectal cancer 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 metastatic colorectal cancer 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).
Second-line Metastatic Colorectal Cancer in Patients who Have
Progressed on an Avastin Containing Regimen in First-line mCRC
In this second-line trial, no new safety signals were observed when
Avastin was administered in second-line mCRC patients who progressed on
an Avastin containing regimen in first-line mCRC. The safety data was
consistent with the known safety profile established in first and
For full Prescribing Information and Boxed WARNINGS on Avastin, please
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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.
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