�ImClone Systems Incorporated (NASDAQ: IMCL) announced overall survival results from BMS CA225-099 (BMS-099), an open-label Phase 3 study of ERBITUX� (cetuximab) in combination with a taxane and carboplatin in the first-line treatment of all histological subtypes of advanced non-small electric cell lung cancer (NSCLC).
These results pertaining to overall survival, a secondary termination, are an update to the antecedently reported results for progression-free survival (PFS), the study's primary endpoint, which were announced in June 2007. The sketch did non meet its primary terminus of PFS, as assessed by an independent radiology review citizens committee (IRRC). Response rate, as assessed by the IRRC, and PFS, as assessed by clinical investigators, were statistically significant and favored the ERBITUX-containing arm.
In this recently completed depth psychology of BMS-099, median overall survival in patients receiving ERBITUX in combination with a taxane and carboplatin was 9.7 months, compared to 8.4 months with chemotherapy alone, with a hazard ratio of 0.89 [95% CI = 0.75-1.05], p=0.17.
The results from this boilers suit survival analysis did not reach statistical significance. BMS-099, a 676-patient study, was not powered to observe an improvement in overall survival with the same degree of statistical preciseness as was the larger 1,125-patient pivotal FLEX (First-line in Lung malignant neoplastic disease with ErbituX) multinational Phase 3 report conducted by Merck KGaA, Darmstadt, Germany. Nonetheless, the BMS-099 survival of the fittest results financial backing those of FLEX, of which boilers suit survival was the primary endpoint.
As recently reported, results from FLEX, demonstrated a statistically significant improvement in overall survival in patients receiving ERBITUX in combination with vinorelbine and cisplatin when compared to chemotherapy (11.3 months vs 10.1 months) with a hazard proportion of 0.871 [95% CI = 0.762-0.996], p=0.044. ImClone and Bristol-Myers Squibb extend to pursue a regulatory filing with the U.S. Food and Drug Administration for the first-line treatment of patients with ripe NSCLC.
"With less than one in five advanced-stage non-small cell lung crab patients presently receiving biologic-based combination therapy in the first-line setting, ImClone is committed to providing new treatment options to address this unmet medical motivation," said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone Systems.
The BMS-099 subject, performed in the U.S. and Canada, was one of several clinical trials intended to assess the potential of ERBITUX in the treatment of ripe NSCLC. Full BMS-099 survey results, including efficacy and safety, testament be submitted to a major medical meeting later on this class.
About Lung Cancer
The American Cancer Society estimates that in the United States, more than 215,000 people will be diagnosed with lung crab in 2008, which accounts for most 15 percent of all cancer diagnoses. Approximately 87 percent of these patients will be diagnosed with NSCLC, with many organism diagnosed with locally in advance or metastatic disease. Lung cancer is the leading cause of cancer-related death in hands and women, with more than than 161,000 deaths expected to occur in 2008 - accounting for about 29 percent of all cancer deaths. In 2008, it is estimated that more Americans testament die from lung crab than titty, prostate, and colorectal cancers combined.
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 increase factor receptor (EGFR, HER1, c-ErbB-1). In vitro assays and in vivo brute studies have shown that binding of ERBITUX to the EGFR blocks phosphorylation and activation of receptor-associated kinases, resulting in inhibition of jail cell growth, elicitation of caspase-mediated cell death, and reduced matrix metalloproteinase and vascular endothelial growth factor production. In vitro, ERBITUX behind 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 give tongue to the EGFR. No antitumour effects of ERBITUX were observed in human neoplasm xenografts wanting EGFR expression.
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
ERBITUX (cetuximab), in combination with radiation therapy, is indicated for the initial intervention 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 later failure of both irinotecan- and oxaliplatin-based regimens. ERBITUX, as a single agent, is besides indicated for the treatment of EGFR-expressing metastatic colorectal cancer in patients world Health Organization 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 potency of ERBITUX in combining with irinotecan is based on nonsubjective response rates. Currently, no data ar available that demonstrate an improvement in disease-related symptoms or increased survival with ERBITUX in combination with irinotecan for the discourse of EGFR-expressing metastatic colorectal carcinoma.
Important Safety Information
Grade 3/4 infusion reactions occurred in approximately 3% of patients receiving ERBITUX (cetuximab) in clinical trials, with fateful outcome reported in less than 1 in chiliad. Serious infusion reactions, requiring medical intercession and immediate, permanent discontinuance of ERBITUX, included rapid onset of airway obstruction (bronchospasm, stridor, hoarseness), hypotension, loss of consciousness, and/or cardiac get. Most (90%) of the severe infusion reactions were associated with the commencement infusion of ERBITUX disdain premedication with antihistamines. Caution must be exercised with every ERBITUX infusion, as there were patients wHO experienced their first spartan infusion reaction during by and by infusions. Monitor patients for 1 hour following ERBITUX infusions in a scope with resuscitation equipment and other agents necessary to treat anaphylaxis (eg, adrenalin, corticosteroids, intravenous antihistamines, bronchodilators, and o). Longer observation periods may be needful in patients who require treatment for infusion reactions.
Cardiopulmonary contain 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 regard the use of ERBITUX in combination with radiation therapy in head and neck cancer patients with a story of coronary thrombosis artery disease, congestive bosom failure or arrhythmias in light of these risks. Closely monitor serum electrolytes including blood serum magnesium, potassium, and calcium during and after ERBITUX therapy.
Interstitial lung disease (ILD), which was fatal in unrivalled case, occurred in 4 of 1570 (
In clinical studies of ERBITUX, dermatological toxicities, including acneform efflorescence, skin drying and fissuring, paronychial rubor, 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 3 patients receiving ERBITUX in clinical trials. Severe acneform rash occurred in 1-17% of patients. Acneform rash usually developed inside the start 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 years. Monitor patients receiving ERBITUX for dermatological toxicities and infectious sequelae. Sun exposure may exacerbate these effects.
The refuge of ERBITUX in combination with radiation therapy and cisplatin has not been established. Death and good cardiotoxicity were observed in a single-arm trial with ERBITUX, actinotherapy therapy, and cisplatin (C mg/m2) in patients with locally ripe squamous prison 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 onrush of hypomagnesemia and concomitant electrolyte abnormalities occurred years to months after induction of ERBITUX therapy. Monitor patients sporadically for hypomagnesemia, hypocalcemia and hypokalemia, during, and for at least 8 weeks following the completion of, ERBITUX therapy. Replete electrolytes as necessary.
The boilers suit 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 unnatural: salivary glands (65%/56%), voice box (52%/36%), subcutaneous tissue (49%/45%), mucous membranes (48%/39%), oesophagus (44%/35%), and skin (42%/33%) in the ERBITUX and radiation versus radiation only arms, severally. The relative incidence of mark 3 or 4 recent radiation toxicities were similar between the radiation therapy alone and the ERBITUX plus radiation therapy coat of arms.
In women of accouchement potential, appropriate contraceptive measures must be used during treatment with ERBITUX and for 6 months next the last dose of ERBITUX. ERBITUX should only be exploited 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, dermatological toxicity and radiation dermatitis, sepsis, nephritic failure, interstitial lung disease, and pulmonic embolus.
The most common adverse reactions associated with ERBITUX (incidence greater than or match to 25%) are cutaneous adverse reactions (including rash, pruritus, and nail changes), headache, looseness, and infection.
The nigh frequent inauspicious 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%), weightiness 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 blizzard (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 weapon (incidence greater than or equal to 50%) were fatigue (89%), rash/desquamation (89%), abdominal pain in the neck (59%), and pain-other (51%). The most common grade 3/4 inauspicious events (greater than or equal to 10%) included: fatigue (33%), pain-other (16%), dyspnea (16%), abdominal pain in the neck (14%), infection without neutropenia (13%), rash/desquamation (12%), and other-gastrointestinal (10%).
The nearly frequent inauspicious events seen in patients with metastatic colorectal genus Cancer (n=354) treated with ERBITUX plus irinotecan in clinical trials (incidence greater than or rival 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 rival to 10%) included: diarrhoea (22%), leucopenia (17%), asthenia/malaise (16%), and acneform efflorescence (14%).
About ImClone Systems
ImClone Systems Incorporated is a fully integrated ball-shaped biopharmaceutical company committed to advancing oncology care by developing and commercializing a portfolio of targeted biological treatments intentional 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 ar located in New York City, with additional judicature 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 make up forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and the Federal securities laws. Although the party believes that the expectations reflected in such advanced 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 jutting. Many of these factors are beyond the company's ability to control or predict. Important factors that may cause actual results to take issue 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 innovative statements in this news release, the company claims the protection of the safe harbour for advanced statements contained in the Private Securities Litigation Reform Act of 1995. The company assumes no obligation to update or supplement any modern statements whether as a result of new information, future events or otherwise.
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