Near Doubling of Survival in Wild-Type or "Normal" K-ras Patients Treated with ERBITUX
NEW YORK, USA | October 22, 2008 | ImClone Systems Incorporated (NASDAQ: IMCL) and Bristol-Myers Squibb Company (NYSE: BMY) today announced the publication of study results showing that metastatic colorectal cancer (mCRC) patients with wild-type or "normal" K-ras tumors who were treated with ERBITUX(R) (cetuximab) plus best supportive care (BSC) had a statistically significant increase in overall survival and progression-free survival compared to those treated with BSC alone. Specifically, patients whose tumors had the normal (mutant negative) K-ras gene achieved a near two-fold improvement in overall survival and progression-free survival over patients treated with BSC alone. In patients with mutated K-ras tumors, there was no significant difference in overall or progression-free survival between those treated with ERBITUX plus BSC and those treated with BSC alone.
These analyses build on previously reported results of the study, which demonstrated that treating patients with ERBITUX as a monotherapy plus BSC significantly increased overall survival compared to BSC alone in patients with unknown K-ras status.
The results of the K-ras analysis of the study were published in the October 23, 2008 issue of the New England Journal of Medicine. The data are from a retrospective analysis of the 394 available archived tissue samples from the previously conducted pivotal Phase 3 study NCIC CTG CO.17. These results were announced in June 2008 at the 10th World Congress on Gastrointestinal Cancer in Barcelona, Spain.
— In the 230 patients with normal, non-mutated, wild-type K-ras tumors, median overall survival was 9.5 months for patients
treated with ERBITUX plus BSC, and 4.8 months with BSC alone (Hazard Ratio [HR]=0.55; 95% Confidence Interval [CI]=0.41
to 0.74; p<0.001); median progression-free survival was 3.7 months and 1.9 months, respectively (HR=0.40; 95% CI=0.30 to 0.54; p<0.001).
— In the 164 patients with mutated K-ras tumors, median overall survival was 4.5 months with ERBITUX plus BSC, and 4.6 months with BSC alone (HR=0.98; 95% CI=0.70 to 1.37; p=0.89); median progression-free survival was 1.8 months for both treatment groups (HR=0.99; 95% CI=0.73 to 1.35; p=0.96).
"These results provide critical insight as we progress toward fully understanding the role of K-ras as a predictive biomarker in the treatment of patients with advanced colon cancer," said Christos Karapetis, M.D., the study’s lead investigator from Flinders Medical Centre and Flinders University, Adelaide, Australia.
"These data provide us with important information about which mCRC patients may benefit from ERBITUX," said Maurizio Voi, M.D., Executive Director, Oncology Global Medical Affairs, Bristol-Myers Squibb. "We will continue to study the role of K-ras so that we can understand how best to utilize ERBITUX in treatment regimens for patients with colorectal cancer."
"We are encouraged by a near doubling of both overall survival and progression-free survival times in mCRC ERBITUX-treated patients with wild-type K-ras tumors, which is consistent with the results demonstrated in other randomized studies of ERBITUX in early mCRC treatment settings," said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone. "These results add to the growing body of ERBITUX data and further support the potential use of ERBITUX as an important treatment option for the approximately 60 percent of colorectal cancer patients whose tumors are K-ras wild-type."
About Study NCIC CTG CO.17
The Phase 3 study NCIC CTG CO.17 was designed to compare ERBITUX plus BSC to BSC alone in patients with epidermal growth factor receptor (EGFR)-expressing mCRC whose disease had progressed through treatment with all approved chemotherapy, including irinotecan, oxaliplatin, and fluoropyrimidines. The full analysis of the study results — which demonstrated that treating patients with ERBITUX as a monotherapy plus BSC significantly increased overall survival compared to BSC alone — were previously published in the Nov. 15, 2007 edition of the New England Journal of Medicine. BSC included palliative therapies designed to alleviate pain and treat other effects caused by mCRC.
Of the 572 patients initially enrolled in the previously published study, K-ras mutation status was ascertained in 394 patients (wild-type K-ras: n=230; mutated K-ras: n=164). Baseline characteristics for the 394 K-ras-evaluable patients were similar to that of the overall population.
This independent, multicenter, open-label, randomized study was conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG).
About K-ras
K-ras is a gene that codes for a protein that plays an important role downstream of the EGFR in the signaling pathway.(1) There are two different types of the K-ras gene found in tumors, either normal or non-mutated K-ras, known as wild-type K-ras, or an abnormal, mutated gene known as mutant K-ras. In the mutant K-ras tumors, the K-ras gene is constitutively activated resulting in continuous signaling independent of EGFR activation. Approximately 60 percent of patients with colorectal cancer are classified as having "normal" or wild-type K-ras status and approximately 40 percent of patients with CRC have a mutated K-ras gene(2).
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 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.
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.
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 a global biopharmaceutical company whose mission is to extend and enhance human life. For more information, visit www.bms.com.
SOURCE: ImClone Systems Incorporated and Bristol-Myers Squibb Company
Post Views: 51
Near Doubling of Survival in Wild-Type or "Normal" K-ras Patients Treated with ERBITUX
NEW YORK, USA | October 22, 2008 | ImClone Systems Incorporated (NASDAQ: IMCL) and Bristol-Myers Squibb Company (NYSE: BMY) today announced the publication of study results showing that metastatic colorectal cancer (mCRC) patients with wild-type or "normal" K-ras tumors who were treated with ERBITUX(R) (cetuximab) plus best supportive care (BSC) had a statistically significant increase in overall survival and progression-free survival compared to those treated with BSC alone. Specifically, patients whose tumors had the normal (mutant negative) K-ras gene achieved a near two-fold improvement in overall survival and progression-free survival over patients treated with BSC alone. In patients with mutated K-ras tumors, there was no significant difference in overall or progression-free survival between those treated with ERBITUX plus BSC and those treated with BSC alone.
These analyses build on previously reported results of the study, which demonstrated that treating patients with ERBITUX as a monotherapy plus BSC significantly increased overall survival compared to BSC alone in patients with unknown K-ras status.
The results of the K-ras analysis of the study were published in the October 23, 2008 issue of the New England Journal of Medicine. The data are from a retrospective analysis of the 394 available archived tissue samples from the previously conducted pivotal Phase 3 study NCIC CTG CO.17. These results were announced in June 2008 at the 10th World Congress on Gastrointestinal Cancer in Barcelona, Spain.
— In the 230 patients with normal, non-mutated, wild-type K-ras tumors, median overall survival was 9.5 months for patients
treated with ERBITUX plus BSC, and 4.8 months with BSC alone (Hazard Ratio [HR]=0.55; 95% Confidence Interval [CI]=0.41
to 0.74; p<0.001); median progression-free survival was 3.7 months and 1.9 months, respectively (HR=0.40; 95% CI=0.30 to 0.54; p<0.001).
— In the 164 patients with mutated K-ras tumors, median overall survival was 4.5 months with ERBITUX plus BSC, and 4.6 months with BSC alone (HR=0.98; 95% CI=0.70 to 1.37; p=0.89); median progression-free survival was 1.8 months for both treatment groups (HR=0.99; 95% CI=0.73 to 1.35; p=0.96).
"These results provide critical insight as we progress toward fully understanding the role of K-ras as a predictive biomarker in the treatment of patients with advanced colon cancer," said Christos Karapetis, M.D., the study’s lead investigator from Flinders Medical Centre and Flinders University, Adelaide, Australia.
"These data provide us with important information about which mCRC patients may benefit from ERBITUX," said Maurizio Voi, M.D., Executive Director, Oncology Global Medical Affairs, Bristol-Myers Squibb. "We will continue to study the role of K-ras so that we can understand how best to utilize ERBITUX in treatment regimens for patients with colorectal cancer."
"We are encouraged by a near doubling of both overall survival and progression-free survival times in mCRC ERBITUX-treated patients with wild-type K-ras tumors, which is consistent with the results demonstrated in other randomized studies of ERBITUX in early mCRC treatment settings," said Eric K. Rowinsky, M.D., Chief Medical Officer and Executive Vice President of ImClone. "These results add to the growing body of ERBITUX data and further support the potential use of ERBITUX as an important treatment option for the approximately 60 percent of colorectal cancer patients whose tumors are K-ras wild-type."
About Study NCIC CTG CO.17
The Phase 3 study NCIC CTG CO.17 was designed to compare ERBITUX plus BSC to BSC alone in patients with epidermal growth factor receptor (EGFR)-expressing mCRC whose disease had progressed through treatment with all approved chemotherapy, including irinotecan, oxaliplatin, and fluoropyrimidines. The full analysis of the study results — which demonstrated that treating patients with ERBITUX as a monotherapy plus BSC significantly increased overall survival compared to BSC alone — were previously published in the Nov. 15, 2007 edition of the New England Journal of Medicine. BSC included palliative therapies designed to alleviate pain and treat other effects caused by mCRC.
Of the 572 patients initially enrolled in the previously published study, K-ras mutation status was ascertained in 394 patients (wild-type K-ras: n=230; mutated K-ras: n=164). Baseline characteristics for the 394 K-ras-evaluable patients were similar to that of the overall population.
This independent, multicenter, open-label, randomized study was conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) in collaboration with the Australasian Gastro-Intestinal Trials Group (AGITG).
About K-ras
K-ras is a gene that codes for a protein that plays an important role downstream of the EGFR in the signaling pathway.(1) There are two different types of the K-ras gene found in tumors, either normal or non-mutated K-ras, known as wild-type K-ras, or an abnormal, mutated gene known as mutant K-ras. In the mutant K-ras tumors, the K-ras gene is constitutively activated resulting in continuous signaling independent of EGFR activation. Approximately 60 percent of patients with colorectal cancer are classified as having "normal" or wild-type K-ras status and approximately 40 percent of patients with CRC have a mutated K-ras gene(2).
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 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.
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.
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 a global biopharmaceutical company whose mission is to extend and enhance human life. For more information, visit www.bms.com.
SOURCE: ImClone Systems Incorporated and Bristol-Myers Squibb Company
Post Views: 51
