- First Study to Demonstrate Survival Benefit with ERBITUX in Patients with
Colorectal Cancer Refractory to All Approved Chemotherapies -
NEW YORK, Nov. 14 /PRNewswire-FirstCall/ -- ImClone Systems
Incorporated (Nasdaq: IMCL) and Bristol-Myers Squibb Company (NYSE: BMY)
announced today results from a multicenter, open-label, randomized Phase
III trial, published in the New England Journal of Medicine, in which
ERBITUX(R) (cetuximab) as a single agent demonstrated a significant
improvement in overall survival in patients with metastatic colorectal
cancer (mCRC) refractory to approved chemotherapy agents. The study
compared ERBITUX plus best supportive care (BSC) to BSC alone in patients
with mCRC whose disease had progressed through treatment with all approved
chemotherapy, including irinotecan, oxaliplatin, and fluoropyrimidines.
The independent study (NCIC CTG CO.17), conducted by the National
Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in
collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG),
involved 572 patients and demonstrated that treating patients with ERBITUX
as a monotherapy plus BSC significantly increased overall survival compared
to BSC alone. BSC included palliative therapies designed to alleviate pain
and treat other effects caused by mCRC.
"This is the first time an antibody used as a single agent in
colorectal cancer has demonstrated an overall survival benefit. These
outcomes add to the growing body of evidence supporting the significant
clinical benefits of ERBITUX," said Eric K. Rowinsky, M.D., Chief Medical
Officer and Senior Vice President of ImClone Systems.
"These data demonstrate that ERBITUX may provide certain colorectal
cancer patients with additional time -- even when other available treatment
options have failed," said Maurizio Voi, M.D., Executive Director, Oncology
Global Medical Affairs, Bristol-Myers Squibb. "The results are part of our
comprehensive clinical development program designed to fully understand the
potential uses of ERBITUX."
The study enrolled patients with epidermal growth factor receptor
(EGFR)- expressing metastatic colorectal cancer who had been previously
treated. ERBITUX was administered at the recommended dose and schedule: 400
mg/m2 initial dose, followed by 250 mg/m2 weekly until disease progression
or unacceptable toxicity.
In this study, the median survival was 6.1 months for patients treated
with ERBITUX plus BSC versus 4.6 months for patients on BSC alone (Hazard
Ratio: 0.77, P=0.005). Treatment with ERBITUX monotherapy resulted in a
significant improvement in progression-free survival versus BSC alone
(Hazard Ratio: 0.68, P<0.001). Twenty-three patients (8.0%) treated with
ERBITUX and no patients on BSC alone had partial responses (P<0.001).
Grade 3/4 adverse events (occurring in greater than or equal to 10% of
patients in either group) reported more frequently in the ERBITUX plus BSC
treatment arm compared with the BSC only arm included fatigue (33% vs 26%),
other pain (16% vs 7%), dyspnea (16% vs 12%), infection without neutropenia
(13% vs 6%) rash/desquamantion (12% vs <1%), and other gastrointestinal
(10% vs 8%). Grade 3/4 infusion reactions (hypersensitivity) occurred in 5%
of patients in the ERBITUX plus BSC arm. The most common (occurring in
greater than or equal to 25% of patients in either group) adverse events of
any grade were rash/desquamation, fatigue, abdominal pain, other pain, dry
skin, dyspnea, constipation, pruritus, diarrhea, vomiting, infection
without neutropenia, headache, fever, insomnia, cough, other dermatology,
and stomatitis.
This study supported the recent label change for ERBITUX -- approved by
the U.S. Food and Drug Administration on October 2, 2007 -- to include
overall survival data as a monotherapy agent in patients with
EGFR-expressing mCRC after failure of irinotecan- and oxaliplatin-based
chemotherapy regimens.
About Colorectal Cancer
In the U.S., approximately 154,000 people will be diagnosed with cancer
of the colon or rectum this year. More than half of these patients have
metastatic disease, or cancer that has spread to other organs, at the time
of diagnosis. EGFR is expressed in 60-80 percent of colorectal cancer
tumors. Colorectal cancer is the third most common cancer in both men and
women, excluding skin cancer.
About ERBITUX(R) (cetuximab)
ERBITUX is a monoclonal antibody (IgG1 Mab) designed to inhibit the
function of a molecular structure expressed on the surface of normal and
tumor cells called the epidermal growth factor receptor (EGFR, HER1,
c-ErbB-1). In vitro assays and in vivo animal studies have shown that
binding of ERBITUX to the EGFR blocks phosphorylation and activation of
receptor-associated kinases, resulting in inhibition of cell growth,
induction of apoptosis, and decreased matrix metalloproteinase and vascular
endothelial growth factor production. In vitro, ERBITUX can mediate
antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor
types. No anti-tumor effects of ERBITUX were observed in human tumor
xenografts lacking EGFR expression. EGFR is part of a signaling pathway
that is linked to the growth and development of many human cancers,
including those of the head and neck, colon and rectum.
ERBITUX, as a single agent, is indicated for the treatment of EGFR-
expressing mCRC after failure of both irinotecan-and oxaliplatin-based
regimens. ERBITUX, as a single agent, is also indicated for the treatment
of EGFR-expressing mCRC in patients who are intolerant to irinotecan-based
regimens.
For full prescribing information, including boxed WARNINGS regarding
infusion reactions and cardiopulmonary arrest, visit
http://www.ERBITUX.com.
Important Safety Information
Grade 3/4 infusion reactions occurred in approximately 3% of patients
receiving ERBITUX (Cetuximab) in clinical trials with fatal outcome
reported in less than 1 in 1000. Reactions characterized by rapid onset of
airway obstruction (bronchospasm, stridor, hoarseness), urticaria,
hypotension, loss of consciousness, and/or cardiac arrest. Severe infusion
reactions require immediate and permanent discontinuation of ERBITUX
therapy
Most reactions (90%) were associated with the first infusion of ERBITUX
despite premedication with antihistamines. Caution must be exercised with
every ERBITUX infusion as there were patients who experienced their first
severe infusion reaction during later infusions. Monitor patients for
1-hour following ERBITUX infusions in a setting with resuscitation
equipment and other agents necessary to treat anaphylaxis (e.g.,
epinephrine, corticosteroids, intravenous antihistamines, bronchodilators,
and oxygen). Longer observation periods may be required in patients who
require treatment for infusion reactions
Severe cases of interstitial lung disease (ILD), which was fatal in one
case, occurred in 4 of 1570 (<0.5%) of patients receiving ERBITUX in
clinical trials. Permanently discontinue ERBITUX where ILD is confirmed.
In clinical studies of ERBITUX, dermatologic toxicities, including
acneform rash, skin drying and fissuring, paronychial inflammation,
infectious sequelae (eg, S. aureus sepsis, abscess formation, cellulitis,
blepharitis, cheilitis), and hypertrichosis occurred in patients receiving
ERBITUX therapy. Acneform rash occurred in 76-88% of 1373 patients
receiving ERBITUX in clinical trials with severe acneform rash occurring in
1-17% of patients. Acneform rash usually developed within the first two
weeks of therapy and resolved in a majority of the patients after cessation
of treatment, although in nearly half, the event continued beyond 28 days.
Monitor patients receiving ERBITUX for dermatologic toxicities and
infectious sequelae. Sun exposure may exacerbate these effects
In women of childbearing potential, appropriate contraceptive measures
must be used during treatment with ERBITUX and for 6 months following the
last dose of ERBITUX. If ERBITUX is used during pregnancy or if patients
become pregnant while receiving ERBITUX, patients should be apprised of the
potential risk for loss of pregnancy or potential hazard to the fetus
Hypomagnesemia occurred in 55% (199/365) of patients receiving ERBITUX
and was severe (NCI CTC grades 3 & 4) in 6-17%. The onset of hypomagnesemia
and accompanying electrolyte abnormalities occurred days to months after
initiation of ERBITUX. Monitor patients periodically for hypomagnesemia,
hypocalcemia and hypokalemia, during and for at least 8 weeks following the
completion of ERBITUX. Replete electrolytes as necessary
The most serious adverse reactions associated with ERBITUX in mCRC
patients are infusion reactions, dermatologic toxicity, sepsis, renal
failure, interstitial lung disease, and pulmonary embolus.
The most common adverse reactions with ERBITUX (incidence greater than
or equal to 25% in the ERBITUX + plus best supportive care arm (BSC))
(n=288) vs. BSC (n=274), respectively, were fatigue (89%, 76%),
rash/desquamation (89%, 16%), abdominal pain (59%, 52%), pain-other (51%,
34%), dry skin (49%, 11%), dyspnea (48%, 43%), constipation (46%, 38%),
pruritus (40%, 8%), diarrhea (39%, 20%), vomiting (37%, 29%), infection
without neutropenia (35%, 17%), headache (33%, 11%), fever (30%, 18%),
insomnia (30%, 15%), cough (29%, 19%), dermatology-other (27%, 6%), and
stomatitis (25%, 10%).
About ImClone Systems
ImClone Systems Incorporated is a fully integrated biopharmaceutical
company committed to advancing oncology care by developing and
commercializing a portfolio of targeted biologic treatments designed to
address the medical needs of patients with a variety of cancers. The
Company's research and development programs include growth factor blockers
and angiogenesis inhibitors. ImClone Systems' headquarters and research
operations are located in New York City, with additional administration and
manufacturing facilities in Branchburg, New Jersey. For more information
about ImClone Systems, please visit the Company's web site at
http://www.imclone.com.
ERBITUX(R) is a registered trademark of ImClone Systems Incorporated.
Certain matters discussed in this news release may constitute
forward-looking statements within the meaning of the Private Securities
Litigation Reform Act of 1995 and the Federal securities laws. Although the
company believes that the expectations reflected in such forward-looking
statements are based upon reasonable assumptions it can give no assurance
that its expectations will be achieved. Forward-looking information is
subject to certain risks, trends and uncertainties that could cause actual
results to differ materially from those currently expected. Many of these
factors are beyond the company's ability to control or predict. Important
factors that may cause actual results to differ materially and could impact
the company and the statements contained in this news release can be found
in the company's filings with the Securities and Exchange Commission,
particularly those factors identified as "risk factors" in the Company's
most recent annual report of Form 10-K and in its quarterly reports on Form
10-Q and current reports on Form 8-K. For forward-looking statements in
this news release, the company claims the protection of the safe harbor for
forward-looking statements contained in the Private Securities Litigation
Reform Act of 1995. The company assumes no obligation to update or
supplement any forward-looking statements whether as a result of new
information, future events or otherwise.
About Bristol-Myers Squibb
Bristol-Myers Squibb is dedicated to the discovery, development and
exhaustive exploration of innovative cancer fighting therapies that extend
and enhance the lives of patients living with cancer. More than 40 years
ago, Bristol-Myers Squibb built a unified vision for the future of cancer
treatment. With expertise, dedication and resolve, that vision led to the
development of a diverse global portfolio of anti-cancer therapies that are
an important cornerstone of care today. Hundreds of scientists in
Bristol-Myers Squibb's Research & Development organization are studying
ways to improve current cancer treatments and identify better, more
effective medicines for the future.
Bristol-Myers Squibb is a global pharmaceutical and related health care
products company whose mission is to extend and enhance human life.
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding product development. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and could
cause actual outcomes and results to differ materially from current
expectations. No forward-looking statement can be guaranteed.
Forward-looking statements in this press release should be evaluated
together with the many uncertainties that affect Bristol-Myers Squibb's
business, particularly those identified in the cautionary factors
discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the
year ended December 31, 2006, in our Quarterly Reports on Form 10-Q and our
Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation
to publicly update any forward-looking statement, whether as a result of
new information, future events or otherwise.
SOURCE Bristol-Myers Squibb; ImClone Systems Incorporated
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Related links:
http://www.bms.com
http://www.imclone.com http://www.ERBITUX.com
CONTACT:
Rebecca Gregory, +1-646-638-5058,
Rebecca.Gregory@imclone.com, or Tracy Henrikson, +1-908-243-9945,
Tracy.Henrikson@imclone.com, both Corporate Communications of
ImClone Systems Incorporated; or Media, Madeline Malia,
+1-609-252-3347, Madeline.Malia@bms.com, or Tony Plohoros,
+1-609-252- 7938, Tony.Plohoros@bms.com, or Investors, John
Elicker, +1-212-546-3775, John.Elicker@bms.com, all of
Bristol-Myers Squibb
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