Vectibix in Combination With Chemotherapy Significantly Improved Progression-Free Survival in First-Line Metastatic Colorectal Cancer
Pivotal Study Meets Primary Endpoint of Progression-Free Survival in Wild-Type KRAS Population Phase 3 Results Reinforce Importance of KRAS Testing
THOUSAND OAKS, Calif., Aug. 6 /PRNewswire-FirstCall/ -- Amgen
(NASDAQ:
AMGN) today announced that Vectibix (panitumumab), administered
in combination with FOLFOX (an oxaliplatin-based chemotherapy),
significantly prolonged progression-free survival (PFS) compared
with FOLFOX alone in the first-line treatment of patients with KRAS
wild-type metastatic colorectal cancer (mCRC).
"We believe that these data document an important advance for
patients with metastatic colorectal cancer," said Roger M.
Perlmutter, M.D., Ph.D., executive vice president of Research and
Development at Amgen. "These are the first prospective Phase 3 data
to demonstrate the utility of KRAS mutational analysis as a
predictive biomarker."
Overall, the adverse event profile was as anticipated for an
anti-EGFR antibody in combination with oxaliplatin-based
chemotherapy, including known events such as skin toxicity,
hypomagnesemia and diarrhea.
Originally designed to compare the treatment effect in the
overall population, the study was amended to analyze outcomes with
respect to the presence or absence of activating mutations in KRAS
in the tumor itself. Tumor KRAS status was ascertained in more than
90 percent of the 1,183 patients enrolled in the trial.
Importantly, in patients with tumors harboring activating KRAS
mutations, PFS was significantly inferior in the Vectibix arm.
These data confirm previous findings when oxaliplatin-based
chemotherapy and an anti-EGFR antibody are combined.
"Our study underscores the importance of KRAS status in
identifying the appropriate patient population to be treated with
Vectibix, consistent with worldwide labeling," said Perlmutter.
"Not only is the improvement in progression-free survival limited
to patients with wild-type KRAS tumors, but patients with KRAS
mutant tumors were negatively affected when Vectibix was added to a
standard chemotherapy regimen. We believe Vectibix should not be
used in patients with tumors containing activating KRAS
mutations."
Detailed efficacy and safety data according to KRAS status will
be submitted for presentation at an upcoming medical
congress.
Study Design
PRIME (Panitumumab Randomized trial In combination with
chemotherapy for Metastatic colorectal cancer to determine
Efficacy) enrolled 1,183 patients globally. Patients were
randomized to receive either 6.0 mg/kg of Vectibix and FOLFOX4 once
every two weeks (Q2W) or FOLFOX4 alone Q2W. The primary endpoint of
the study is progression-free survival by KRAS status and secondary
endpoints include overall survival, objective response rate, time
to progression, duration of response and safety. Long-term follow
up for overall survival is ongoing.
About KRAS
Results from studies performed over the last twenty-five years
indicate that KRAS plays an important role in cell growth
regulation. In mCRC, EGFR transmits signals through a set of
intracellular proteins. Upon reaching the nucleus, these signals
instruct the cancer cell to reproduce and metastasize, leading to
cancer progression. Anti-EGFR antibody therapies work by blocking
the activation of EGFR, thereby inhibiting downstream events that
lead to malignant signaling. However, it is hypothesized that in
patients whose tumors harbor a mutated KRAS gene, the KRAS protein
is always turned "on," regardless of whether the EGFR has been
activated or therapeutically inhibited. KRAS mutations occur in
approximately 40 - 50 percent of mCRC.
About Colorectal Cancer
Colorectal cancer is the fourth most common cancer in men and
the third most common cancer in women worldwide. In 2007,
approximately 1.2 million cases of colorectal cancer were expected
to occur globally. With more than 630,000 deaths worldwide per
year, it is the second leading cause of cancer-related death in the
Western world. The highest incidence rates are found in Japan,
North America, parts of Europe, New Zealand, and Australia, and
rates are low in Africa and South-East Asia. Rates are
substantially higher in men than in women.
About Vectibix
Vectibix is the first fully human anti-EGFR antibody approved by
the U.S. Food and Drug Administration (FDA) for the treatment of
mCRC. Vectibix was approved in the United States in September 2006
as a monotherapy for the treatment of patients with EGFR expressing
mCRC after disease progression on or following fluoropyrimidine-,
oxaliplatin-, and irinotecan-containing chemotherapy
regimens.
The effectiveness of Vectibix as a single agent for the
treatment of EGFR-expressing, metastatic colorectal carcinoma is
based on progression-free survival. Currently no data are available
that demonstrate an improvement in disease-related symptoms or
increased survival with Vectibix. Vectibix has not shown a
treatment benefit for patients whose tumors had KRAS mutations in
codon 12 or 13.
In December 2007, the EMEA granted a conditional marketing
authorization for Vectibix as monotherapy for the treatment of
patients with EGFR-expressing mCRC with wild-type KRAS genes after
failure of standard chemotherapy regimens. Vectibix has been
launched in over 20 countries, Switzerland, Australia and Canada.
Applications in the rest of the world are pending.
Important Product Safety Information
Dermatologic Toxicity: Dermatologic toxicities occurred in 89
percent of patients and were severe (NCI-CTC grade 3 and higher) in
12 percent of patients receiving Vectibix monotherapy. Withhold
Vectibix for dermatologic toxicities that are grade 3 or higher or
are considered intolerable. If toxicity does not improve to less
than or equal to grade 2 within 1 month, permanently discontinue
Vectibix. The clinical manifestations included, but were not
limited to, dermatitis acneiform, pruritus, erythema, rash, skin
exfoliation, paronychia, dry skin, and skin fissures. Subsequent to
the development of severe dermatologic toxicities, infectious
complications, including sepsis, septic death, and abscesses
requiring incisions and drainage were reported.
Infusion Reactions: Severe infusion reactions occurred in
approximately 1 percent of patients. Severe infusion reactions
included anaphylactic reactions, bronchospasm, and hypotension.
Although not reported with Vectibix, fatal infusion reactions have
occurred with other monoclonal antibody products. Stop infusion if
a severe infusion reaction occurs. Depending on the severity and/or
persistence of the reaction, permanently discontinue
Vectibix.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative
human therapeutics. A biotechnology pioneer since 1980, Amgen was
one of the first companies to realize the new science's promise by
bringing safe and effective medicines from lab, to manufacturing
plant, to patient. Amgen therapeutics have changed the practice of
medicine, helping millions of people around the world in the fight
against cancer, kidney disease, rheumatoid arthritis, and other
serious illnesses. With a deep and broad pipeline of potential new
medicines, Amgen remains committed to advancing science to
dramatically improve people's lives. To learn more about our
pioneering science and our vital medicines, visit
www.amgen.com.
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CONTACT: Amgen, Thousand Oaks Christine Regan: 805-447-5476 (media) Arvind Sood: 805-447-1060 (investors) (Logo: http://www.newscom.com/cgi-bin/prnh/20081015/AMGENLOGO)
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Source: Amgen
CONTACT: media, Christine Regan, +1-805-447-5476, or investors,
Arvind
Sood, +1-805-447-1060, both of Amgen
Web Site: http://www.amgen.com/
Posted: August 2009
