Amgen Announces Overall Survival Results for Vectibix(R) in First-Line
Metastatic Colorectal Cancer
Phase 3 Results Reinforce Importance of KRAS Status
THOUSAND OAKS, Calif., Nov. 5 /PRNewswire-FirstCall/ -- Amgen (Nasdaq: AMGN)
today announced that the Phase 3 PRIME "203" trial evaluating Vectibix®
(panitumumab) administered in combination with FOLFOX (an oxaliplatin-based
chemotherapy) as a first-line treatment of metastatic colorectal cancer (mCRC)
failed to meet a secondary endpoint of overall survival. Earlier this year,
it was announced that the trial met its primary endpoint by significantly
prolonging progression-free survival (PFS) in the first-line treatment of
patients with KRAS wild-type mCRC.
The prospective analysis of the 203 study showed that Vectibix, when added to
a FOLFOX chemotherapy regimen in patients with KRAS wild-type mCRC, resulted
in a median overall survival of 23.9 months compared to 19.7 months for
patients treated with FOLFOX alone. The median overall survival difference of
4.2 months in the Vectibix arm did not reach statistical significance
(HR=0.83, p=0.072).
"As we previously announced, the 203 study met its primary endpoint of
progression-free survival in the first-line treatment of patients with KRAS
wild-type metastatic colorectal cancer," said Roger M. Perlmutter, M.D.,
Ph.D., executive vice president of Research and Development at Amgen. "While
not statistically significant, we are also encouraged by the positive trend of
the data for overall survival for these patients treated with Vectibix."
Overall survival appeared to be reduced in patients with KRAS mutant tumors
receiving Vectibix. Although not statistically significant, this result
emphasizes the importance, as described in product labeling, of ensuring that
patients receiving Vectibix( )do not bear tumors containing KRAS mutations.
Overall, the adverse event profile was as anticipated for an anti-EGFR
antibody in combination with oxaliplatin-based chemotherapy, including known
events such as rash, diarrhea and hypomagnesemia. Vectibix-related grade 3
infusion reactions were reported for two patients (less than 1 percent).
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.
Available results from the trial were presented earlier this year at the 2009
ECCO 15 - ESMO 34 European Multidisciplinary Congress in Berlin, Germany
showing that Vectibix significantly improved median progression-free survival
by 1.6 months (9.6 versus 8.0 months for patients treated with FOLFOX alone,
in patients with KRAS wild-type mCRC (primary endpoint). Further, the addition
of Vectibix to chemotherapy also improved response rate in the KRAS wild-type
patient population as measured by blinded central review (55 percent versus 48
percent in the FOLFOX only arm).
The data for the 203 study has been submitted for consideration of
presentation at the American Society of Clinical Oncology - The
Gastrointestinal Cancers Symposium Meeting for 2010.
Study Design
Patients enrolled in the "203" or PRIME trial (Panitumumab Randomized trial in
combination with chemotherapy for Metastatic colorectal cancer to determine
Efficacy) 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.
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
