RTOG Study: Adding Cetuximab to Chemotherapy and Radiotherapy Leads to Improved Outcome...

RTOG Study: Adding Cetuximab to Chemotherapy and Radiotherapy Leads to Improved Outcome for Lung Cancer Patients

Survival Results Better Than Any Previously Reported by RTOG
CHICAGO--(Business Wire)--
Radiation Therapy Oncology Group (RTOG) investigators and ImClone
Systems Incorporated (Nasdaq: IMCL) today announced that adding the
biologic agent cetuximab (ERBITUX(R)) to chemotherapy and radiotherapy
for patients with inoperable non-small cell lung cancer (NSCLC)
resulted in higher median survival rates and two-year overall survival
rates than previous RTOG studies in patients with Stage III A/B
inoperable NSCLC. Investigators for RTOG, an NCI-funded national
cooperative clinical trials group and clinical research enterprise
component of the American College of Radiology (ACR), presented their
results today at the American Society of Clinical Oncology's 44th
Annual Meeting in Chicago.

Cetuximab is an IgG1 monoclonal antibody that targets the
epidermal growth factor receptor (EGFR), thereby inhibiting cancer
cell growth and proliferation. Cetuximab has been shown to enhance the
activity of radiation therapy.

The phase II study of 87 evaluable patients with Stage IIIA/B
inoperable NSCLC, RTOG 0324, showed a median survival of 22.7 months
and a 2-year overall survival rate of 49.3% which are higher than
those achieved in past RTOG studies. According to George Blumenschein,
M.D., the study principal investigator from The University of Texas
M.D. Anderson Cancer Center, "The combination of cetuximab and
chemoradiotherapy is well tolerated and shows promise. Further phase
III testing in the multicenter setting is warranted."

Patients entered in the multicenter trial received an initial dose
of cetuximab followed by 7 weeks of cetuximab given concurrently with
weekly doses of paclitaxel and carboplatin and 7 weeks of daily
radiotherapy. Patients then received cetuximab once a week for 3 weeks
followed by consolidation therapy of 6 weeks of cetuximab, paclitaxel,
and carboplatin administered once a week. Adverse events related to
the treatment were acceptable with 17 patients experiencing grade 4
hematologic toxicity and 7 patients with grade 3 esophagitis.

"We are very excited by these RTOG study results, which show that
the addition of cetuximab to chemoradiation produced a considerable
improvement in survival compared to previous RTOG studies of various
therapeutic regimens in this setting. Additionally, the cetuximab
chemoradiation regimen had a similar safety profile to that expected
from chemoradiation alone," said Eric K. Rowinsky, M.D., Executive
Vice President and Chief Medical Officer of ImClone. "These data also
reinforce the positive data seen with cetuximab in non-small cell lung
cancer and can serve as a foundation for further evaluations of
cetuximab with chemoradiation in earlier stages."

"RTOG has long been at the forefront in testing novel agents with
radiotherapy," relates Walter J. Curran, Jr., the RTOG Group Chair,
and the Lawrence W. Davis Professor and Chair of the Department of
Radiation Oncology in the Emory School of Medicine and Chief Medical
Officer of the Emory Winship Cancer Institute. "This trial is another
example of RTOG's commitment to advancing multi-modality cancer
research."

Lung cancer is expected to account for 162,000 deaths in 2008,
making it the leading cause of cancer mortality for both men and
women.

ASCO Abstract #7516, A Phase II Study of Cetuximab (C225) In
Combination with Chemoradiation (CRT) in Patients (PTS) with Stage
IIIA/B Non-Small Cell Lung Cancer (NSCLC): A Report of the 2 Year and
Median Survival (MS) for the RTOG 0324 Trial, is available at
http://www.abstract.asco.org/AbstView_55_36161.html.

Information about RTOG is available at www.rtog.org. A copy of the
research protocol is available at
http://www.rtog.org/members/protocols/0324/0324.pdf.

In addition to Dr. Blumenschein, authors include: R. Paulus, RTOG
Headquarters, Philadelphia, PA; W. Curran, Emory University School of
Medicine; F. Robert, University of Alabama at Birmingham, Birmingham,
AL; F. Fossella and R. Komaki, The University of Texas M. D. Anderson
Cancer Center, Houston, TX; M. Werner-Wasik, Thomas Jefferson
University Hospital, Philadelphia, PA; P. Doescher, Medical College of
Wisconsin, Milwaukee, WI; and H. Choy, The University of Texas
Southwestern, Dallas, TX. The research was funded by National Cancer
Institute grants CA21661, CA37422, and 32115.

The cetuximab used in this study was prepared by ImClone Systems
Incorporated and supplied by the Bristol-Myers Squibb (BMS) Company to
patients free of charge.

The Radiation Therapy Oncology Group (RTOG) is a clinical research
enterprise of the American College of Radiology (ACR), located in the
ACR Philadelphia, PA office. RTOG is a multi-institutional
international clinical cooperative group funded primarily by National
Cancer Institute grants CA21661, CA32115 and CA37422. RTOG has 40
years of experience in conducting clinical trials and is comprised of
over 300 major research institutions in the United States, Canada, and
internationally. The group is currently accruing to 40 studies that
involve radiation therapy alone or in conjunction with surgery and/or
chemotherapeutic drugs which investigate quality of life issues and
their effects on the cancer patient.

The American College of Radiology (ACR) is a national professional
organization serving more than 32,000 radiologists, radiation
oncologists, interventional radiologists and medical physicists with
programs focusing on the practice of radiology and the delivery of
comprehensive health care services.

About ERBITUX(R) (Cetuximab)

ERBITUX (cetuximab) 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. In
vitro assays and in vivo animal studies have shown that cetuximab
inhibits the growth and survival of tumor cells that express the EGFR.
No anti-tumor effects of cetuximab were observed in human tumor
xenografts lacking EGFR expression.

Squamous Cell Carcinoma of the Head and Neck (SCCHN)

ERBITUX, in combination with radiation therapy, is indicated for
the initial treatment of locally or regionally advanced squamous cell
carcinoma of the head and neck. ERBITUX, as a single agent, is
indicated for the treatment of patients with recurrent or metastatic
squamous cell carcinoma of the head and neck for whom prior
platinum-based therapy has failed.

Colorectal Cancer

ERBITUX, as a single agent, is indicated for the treatment of
EGFR-expressing metastatic colorectal cancer after failure of both
irinotecan- and oxaliplatin-based regimens. ERBITUX, as a single
agent, is also indicated for the treatment of EGFR-expressing
metastatic colorectal cancer in patients who are intolerant to
irinotecan-based regimens.

ERBITUX, in combination with irinotecan, is indicated for the
treatment of EGFR-expressing metastatic colorectal carcinoma in
patients who are refractory to irinotecan-based chemotherapy. The
effectiveness of ERBITUX in combination with irinotecan is based on
objective response rates. Currently, no data are available that
demonstrate an improvement in disease-related symptoms or increased
survival with ERBITUX in combination with irinotecan for the treatment
of EGFR-expressing metastatic colorectal carcinoma.

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. Serious infusion reactions,
requiring medical intervention and immediate, permanent
discontinuation of ERBITUX, included rapid onset of airway obstruction
(bronchospasm, stridor, hoarseness), hypotension, loss of
consciousness, and/or cardiac arrest. 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 (eg, epinephrine,
corticosteroids, intravenous antihistamines, bronchodilators, and
oxygen). Longer observation periods may be required in patients who
require treatment for infusion reactions.

Cardiopulmonary arrest and/or sudden death occurred in 4 (2%) of
208 patients with squamous cell carcinoma of the head and neck treated
with radiation therapy and ERBITUX, as compared to none of 212
patients treated with radiation therapy alone. Fatal events occurred
within 1 to 43 days after the last ERBITUX treatment. Carefully
consider the use of ERBITUX in combination with radiation therapy in
head and neck cancer patients with a history of coronary artery
disease, congestive heart failure or arrhythmias in light of these
risks. Closely monitor serum electrolytes including serum magnesium,
potassium, and calcium during and after ERBITUX therapy.

Interstitial lung disease (ILD), which was fatal in one case,
occurred in 4 of 1570 (less than 0.5%) patients receiving ERBITUX in
clinical trials. Interrupt ERBITUX for acute onset or worsening of
pulmonary symptoms. 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. Severe acneform
rash occurred 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.

The safety of ERBITUX in combination with radiation therapy and
cisplatin has not been established. Death and serious cardiotoxicity
were observed in a single-arm trial with ERBITUX, radiation therapy,
and cisplatin (100 mg/m2) in patients with locally advanced squamous
cell carcinoma of the head and neck. Two of 21 patients died, one as a
result of pneumonia and one of an unknown cause. Four patients
discontinued treatment due to adverse events. Two of these
discontinuations were due to cardiac events.

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 therapy. Monitor patients
periodically for hypomagnesemia, hypocalcemia and hypokalemia, during,
and for at least 8 weeks following the completion of, ERBITUX therapy.
Replete electrolytes as necessary.

The overall incidence of late radiation toxicities (any grade) was
higher with ERBITUX in combination with radiation therapy compared
with radiation therapy alone. The following sites were affected:
salivary glands (65%/56%), larynx (52%/36%), subcutaneous tissue
(49%/45%), mucous membranes (48%/39%), esophagus (44%/35%), and skin
(42%/33%) in the ERBITUX and radiation versus radiation alone arms,
respectively. The incidence of grade 3 or 4 late radiation toxicities
were similar between the radiation therapy alone and the ERBITUX plus
radiation therapy arms.

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. ERBITUX should only be used during
pregnancy if the potential benefit justifies the potential risk to the
fetus.

The most serious adverse reactions associated with ERBITUX across
all studies were infusion reactions, cardiopulmonary arrest,
dermatologic toxicity and radiation dermatitis, sepsis, renal failure,
interstitial lung disease, and pulmonary embolus.

The most common adverse reactions associated with ERBITUX
(incidence greater than or equal to 25%) are cutaneous adverse
reactions (including rash, pruritus, and nail changes), headache,
diarrhea, and infection.

The most frequent adverse events seen in patients with carcinomas
of the head and neck receiving ERBITUX in combination with radiation
therapy (n=208) versus radiation alone (n=212) (incidence greater than
or equal to 50%) were acneform rash (87%/10%), radiation dermatitis
(86%/90%), weight loss (84%/72%), and asthenia (56%/49%). The most
common grade 3/4 adverse events (greater than or equal to 10%)
included: radiation dermatitis (23%), acneform rash (17%), and weight
loss (11%).

The most frequent adverse events seen in patients with metastatic
colorectal cancer (n=288) in the ERBITUX + best supportive care arm
(incidence greater than or equal to 50%) were fatigue (89%),
rash/desquamation (89%), abdominal pain (59%), and pain-other (51%).
The most common grade 3/4 adverse events (greater than or equal to
10%) included: fatigue (33%), pain-other (16%), dyspnea (16%),
abdominal pain (14%), infection without neutropenia (13%),
rash/desquamation (12%), and gastrointestinal-other (10%).

The most frequent adverse events seen in patients with metastatic
colorectal cancer (n=354) treated with ERBITUX plus irinotecan in
clinical trials (incidence greater than or equal to 50%) were acneform
rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea (55%).
The most common grade 3/4 adverse events (greater than or equal to
10%) included: diarrhea (22%), leukopenia (17%), asthenia/malaise
(16%), and acneform rash (14%).

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 projected. 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,
including quarterly reports on Form 10-Q, current reports on Form 8-K
and annual reports on Form 10-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.

Radiation Therapy Oncology Group
Sharon Hartson Stine, 609-458-5604 (Mobile)
shartson@phila.acr.org
or
ImClone Systems Incorporated
Tracy Henrikson, 609-240-3902 (Mobile)
tracy.henrikson@imclone.com

Copyright Business Wire 2008