NEW YORK--(BUSINESS WIRE)--ImClone Systems Incorporated (NASDAQ: IMCL - News) and Bristol-Myers Squibb Company (NYSE: BMY - News) today announced five-year overall survival data from the pivotal Phase 3 study examining ERBITUX® (cetuximab) combined with radiation in patients with locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN). These results were presented today at the American Society for Therapeutic Radiology and Oncology (ASTRO) Annual Meeting in Boston.
Analysis of these five-year data demonstrate that the addition of ERBITUX to radiation therapy resulted in a significant increase in median overall survival for patients with SCCHN, when compared to radiation therapy alone [49.0 vs. 29.3 months, respectively; p=0.018, Hazard Ratio (HR)=0.725, 95% CI (0.556-0.946)]. The overall survival rate at five years was 45 percent vs. 36 percent, respectively (p=0.018); survival rate at three years was 55 percent vs. 45 percent (p=0.05), respectively. These data are consistent with results in the current head and neck labeling for ERBITUX, which include the median overall survival rate [49.0 vs. 29.3 months, respectively; p=0.03, HR=0.74, 95% CI (0.57-0.97)].
“ERBITUX in combination with radiation demonstrated a statistically significant improvement in overall survival versus radiation alone at five years,” said James Bonner, M.D., University of Alabama, principal investigator for the study. “These results are important for both physicians and patients because this is a difficult type of cancer to treat.”
The international, randomized study (IMCL-9815), conducted by ImClone and its partner Merck KGaA, Darmstadt, Germany, enrolled 424 previously untreated patients with locally or regionally advanced squamous cell carcinoma of the oropharynx (area of the throat at the back of the mouth), larynx (voice box) or hypopharynx (cavity at the back of the mouth that opens into the esophagus) that has spread through the head and neck region. Patients were randomly assigned to receive ERBITUX plus radiation (n=211) or radiation alone (n=213) for six to seven weeks. ERBITUX was dosed weekly, starting one week before radiation and for the duration of radiation therapy. The median number of ERBITUX doses administered in the clinical study was eight (1-11 infusions). As part of this pre-specified analysis, patients were evaluated during semi-annual follow-up exams during years three through five.
“These updated five-year overall survival data further support our belief in ERBITUX as the first biologic approved to treat head and neck cancer in more than 30 years, and are part of a comprehensive clinical development program designed to fully understand the potential uses of ERBITUX for cancer patients,” said Maurizio Voi, M.D., Executive Director, Oncology Global Medical Affairs, Bristol-Myers Squibb.
“These data demonstrate the positive clinical benefit that patients with advanced head and neck cancer may achieve with ERBITUX, which is the first biologic ever approved by the FDA for head and neck cancer that showed a survival benefit in locally or regionally advanced SCCHN,” said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone.
A comprehensive safety analysis was not performed at five years. The most common adverse events reported at three years in the ERBITUX plus radiation treatment group included skin rash (87%), mucositis/stomatitis (93%), dysphagia (65%), xerostomia (72%), fatigue/malaise (56%) and infusion reactions (15%). Severe (Grade 3/4) adverse events included skin rash (17%), mucositis/stomatitis (56%), dysphagia (26%), xerostomia (45%), fatigue/malaise (4%) and infusion reactions (3%). With the exception of skin rash and infusion reactions (which were higher in the ERBITUX-treated arm), the incidence of grade 3 or greater toxicity, including mucositis, which often precludes combining new therapies with radiation, did not differ significantly between the treatment arms.
The three-year results from this study and other ERBITUX data were included in regulatory applications in various countries, including a supplemental Biologics License Application (sBLA) approved by the U.S. Food and Drug Administration (FDA) in 2006.
About Head and Neck Cancer
According to the American Cancer Society, 87,290 Americans will be diagnosed with head and neck cancer in 2008, including cancers of the tongue, the rest of the mouth, the salivary glands and inside the throat, the voice box, eye and orbit, thyroid and the lymph nodes in the upper neck. In addition, it is estimated that more than 13,090 Americans will die from this disease this year. Head and neck cancer most often affects people over the age of 50, and men are twice as likely to be diagnosed as women. The most common risk factors are tobacco and excessive alcohol use.
About ERBITUX® (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 ERBITUX inhibits the growth and survival of tumor cells that express the EGFR. No anti-tumor effects of ERBITUX 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
Infusion Reactions
* 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 o 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 (90%) of the severe infusion reactions were associated with the first infusion of ERBITUX despite premedication with antihistamines o Caution must be exercised with every ERBITUX infusion, as there were patients who experienced their first severe infusion reaction during later infusions o 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
* 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 o 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 o Closely monitor serum electrolytes including serum magnesium, potassium, and calcium during and after ERBITUX therapy
Pulmonary Toxicity
-- Interstitial lung disease (ILD), which was fatal in one case, occurred in 4 of 1570 (<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
Dermatologic Toxicities
* 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 o 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 o Monitor patients receiving ERBITUX for dermatologic toxicities and infectious sequelae o Sun exposure may exacerbate these effects
ERBITUX plus Radiation Therapy and Cisplatin
-- 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
Electrolyte Depletion-- 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
Late Radiation Toxicities
* 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
Pregnancy
* 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
Adverse Events
* 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 (>=)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 =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 ((>=)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 = 50%) were fatigue (89%), rash/desquamation (89%), abdominal pain (59%), and pain-other (51%). The most common grade 3/4 adverse events ((>=)10%) included: fatigue (33%), pain-other (16%), dyspnea (16%), abdominal pain (14%), infection without neutropenia (13%), rash/desquamation (12%), and other-gastrointestinal (10%) * The most frequent adverse events seen in patients with metastatic colorectal cancer (n=354) treated with ERBITUX plus irinotecan in clinical trials (incidence = 50%) were acneform rash (88%), asthenia/malaise (73%), diarrhea (72%), and nausea (55%). The most common grade 3/4 adverse events ((>=) 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® 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 a global biopharmaceutical and related health care products company whose mission is to extend and enhance human life.
Contact:
ImClone Systems Incorporated Media: Tracy Henrikson Corporate Communications 908-243-9945 Tracy.Henrikson@imclone.com Investor: Rebecca Gregory Corporate Communications 646-638-5058 Rebecca.Gregory@imclone.com or Bristol-Myers Squibb Media Brian Henry, 609-252-3337 Brian.Henry@bms.com Investors John Elicker, 212-546-3775 John.Elicker@bms.com
Source: Bristol-Myers Squibb
