Vectibix(R) in Combination With Chemotherapy Significantly Improved Progression-Free Survival in First-Line Metastatic Colorecta
August 06 2009 - 4:03PM
PR Newswire (US)
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.
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