Vectibix(R) Significantly Improved Progression-Free Survival in Second-Line Treatment of KRAS Wild-Type Metastatic Colorectal Ca
August 17 2009 - 4:07PM
PR Newswire (US)
Second Prospective Phase 3 Vectibix Combination Chemotherapy Trial
to Show Progression-Free Survival Advantage in KRAS Wild-Type
Population THOUSAND OAKS, Calif., Aug. 17 /PRNewswire-FirstCall/ --
Amgen (NASDAQ: AMGN) today announced positive top-line results from
a Phase 3 trial evaluating Vectibix (panitumumab) in combination
with FOLFIRI (an irinotecan-based chemotherapy) as a second-line
treatment in 1,186 patients with metastatic colorectal cancer
(mCRC). The co-primary endpoints, tested independently, were
progression-free and overall survival. Vectibix significantly
improved progression-free survival in combination with FOLFIRI,
compared to FOLFIRI alone, in patients with KRAS wild-type mCRC.
Although numerically greater, the improvement in median overall
survival did not achieve statistical significance in the Vectibix
arm. The addition of Vectibix had no positive or negative effect on
progression-free or overall survival in patients with tumors
harboring activating KRAS mutations. "With these data, Vectibix has
now demonstrated improved progression-free survival in Phase 3
trials in patients with KRAS wild-type tumors in both first- and
second-line treatment of metastatic colorectal cancer," said Roger
M. Perlmutter, M.D., Ph.D. executive vice president of Research and
Development at Amgen. "These results add to the growing body of
evidence confirming the utility of KRAS as a predictive biomarker."
Overall, the adverse event profile was as anticipated for an
anti-EGFR antibody in combination with irinotecan-based
chemotherapy, including known events such as skin toxicity,
diarrhea and hypomagnesemia. 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 patients enrolled in
this trial. Recently, the Company announced Phase 3 results from a
first-line "203" trial which showed that Vectibix significantly
improved progression-free survival in mCRC patients with KRAS
wild-type tumors in combination with FOLFOX (an oxaliplatin-based
chemotherapy). Detailed efficacy and safety data from both studies
will be presented at Europe's largest cancer conference, ECCO 15 -
ESMO 34, in September 2009. Study Design The "181" trial is a
global, multicenter, randomized, double-blind, placebo-controlled
Phase 3 study. Patients enrolled in the study (n=1,186) were
randomized to receive either 6.0 mg/kg of Vectibix and FOLFIRI
every two weeks (Q2W) or FOLFIRI alone Q2W. The independently
tested co-primary endpoints are progression-free survival and
overall survival. Secondary endpoints include objective response
rate, time to progression, duration of response and safety by KRAS
status. 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, the 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 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 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. In December 2007, the
EMEA granted a conditional marketing authorization for Vectibix as
monotherapy for the treatment of patients with EGFR-expressing
metastatic colorectal cancer (mCRC) with wild-type KRAS genes after
failure of standard chemotherapy regimens. Vectibix has been
launched in over 20 countries, including Switzerland, Australia and
Canada. Applications in the rest of the world are pending. 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.
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
http://www.amgen.com/. Forward-Looking Statements This news release
contains forward-looking statements that are based on management's
current expectations and beliefs and are subject to a number of
risks, uncertainties and assumptions that could cause actual
results to differ materially from those described. All statements,
other than statements of historical fact, are statements that could
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those discussed below and more fully described in the Securities
and Exchange Commission (SEC) reports filed by Amgen, including
Amgen's most recent annual report on Form 10-K and most recent
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otherwise noted, Amgen is providing this information as of Aug. 17,
2009 and expressly disclaims any duty to update information
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discussed in this news release. CONTACT: Amgen, Thousand Oaks
Christine Regan: 805-447-5476 (media) Arvind Sood: 805-447-1060
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Thousand Oaks, media, Christine Regan, +1-805-447-5476, or
investors, Arvind Sood, +1-805-447-1060, both of Amgen Web Site:
http://www.amgen.com/
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