Vectibix(R) Significantly Improved Progression-Free Survival in Second-Line Treatment of KRAS Wild-Type Metastatic Colorectal Cancer
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.
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.
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.
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
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
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.
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CONTACT: Amgen, Thousand Oaks
Christine Regan: 805-447-5476 (media)
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