DARMSTADT, Germany/AMSTERDAM, The Netherlands I September 28, 2013 I Merck Serono, the biopharmaceutical division of Merck, today announced that the German cooperative investigator group AIO (Arbeitsgemeinschaft Internistische Onkologie) reported new data from the Phase III head-to-head clinical trial FIRE-3, which show a clinically relevant improvement from Erbitux® (cetuximab) plus FOLFIRI versus bevacizumab plus FOLFIRI as 1st line treatment in metastatic colorectal cancer (mCRC) in patients with RAS wild-type tumors.1
The new data, from a preplanned exploratory analysis, were presented at the European Cancer Congress 2013 (ECCO-ESMO-ESTRO). The analysis shows a 7.5-month increase in median overall survival (OS) in mCRC patients with RAS wild-type tumors ((n=342); defined as having no mutations in exons 2, 3 and 4 of KRAS and NRAS), receiving 1st line Erbitux plus FOLFIRI compared with patients receiving bevacizumab plus FOLFIRI (OS: 33.1 months vs. 25.6 months, respectively; hazard ratio [HR]: 0.70; p=0.011). In a post hoc analysis of the patient group with any RAS mutations (n=178), patients who received Erbitux plus FOLFIRI 1st line reached an OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab plus FOLFIRI (HR: 1.09; p=0.60).1
As previously presented at the annual meeting of the American Society of Clinical Oncology (ASCO) 2013 and at the World Congress on Gastrointestinal Cancer 2013, the primary endpoint of the trial, objective response rate based on investigators’ read in patients with KRAS exon 2 wild-type tumors, was not met.2,3 In the patient group with KRAS exon 2 wild-type tumors, an expected and balanced cross-over or continuation beyond progression with regard to subsequent biologic treatments in 2nd line therapy (either EGFR antibody or bevacizumab) was observed. Also, no major imbalances were noted with regard to chemotherapies used in 2nd line treatment. It is important to note that this result is not fully mature (57% event rate in the “intent-to-treat” KRAS exon 2 wild-type population) and will be updated in due course.2
“These new data from the Phase III study FIRE-3 show a 7.5-month increase in median overall survival to 33.1 months when using 1st line Erbitux plus FOLFIRI as compared to using bevacizumab plus FOLFIRI in metastatic colorectal cancer. Such a prolongation is a paradigm shift in mCRC treatment since the introduction of monoclonal antibodies,” said Professor Volker Heinemann from the Ludwig-Maximilians University, Munich, and FIRE-3 principal investigator. “Together with insights from other recent relevant studies, these results suggest that 1st line treatment of RAS wild-type patients should include an anti-EGFR therapy.”
“These results continue to reinforce the value of Erbitux as a 1st line treatment for metastatic colorectal cancer and show that RAS tumor status is likely to help to identify those patients who are most likely to benefit from Erbitux,” said Dr. Annalisa Jenkins, Head of Global Drug Development and Medical for Merck Serono. “Additional biomarker analyses are being conducted on data from the pivotal Erbitux studies, CRYSTAL and OPUS to help shed additional light on the role of RAS mutations in these patients.”
About the FIRE-3 study
FIRE-3 is an independent, randomized, controlled, head-to-head Phase III trial led by Ludwig-Maximilians University in Munich, Germany. Merck Serono GmbH has financially supported the study. The FIRE-3 trial is being conducted in Europe, including 752 mCRC patients of whom 592 patients had confirmed KRAS exon 2 wild-type tumors. Of these, 297 patients were randomized to Erbitux plus FOLFIRI and 295 to bevacizumab plus FOLFIRI.2 113 patients had confirmed KRAS exon 2 mutations.
Initial data from the FIRE-3 study “intent-to-treat” population were presented at ASCO 2013. The primary endpoint, objective response rate (ORR) based on investigators’ read, of the FIRE-3 trial was not met (62% for Erbitux vs. 58% for bevacizumab; odds ratio 1.18).2
Analysis of RAS tumor status1
In the population with samples available for further RAS mutation analyses (n=407;KRAS exons 3 or 4, NRAS exons 2, 3, or 4), 84% of patients have RAS wild-type tumors and 16% RAS mutant tumors (other than KRAS exon 2).
Median OS was 33.1 months in mCRC patients with RAS wild-type tumors (n=342) receiving 1st line Erbitux plus FOLFIRI compared with 25.6 months in patients receiving bevacizumab plus FOLFIRI (HR: 0.70; 95% confidence interval [CI]: 0.53–0.92; p=0.011). ORR was substantially improved (65.5% for Erbitux plus FOLFIRI vs. 59.6% for bevacizumab plus FOLFIRI p=0.157). Progression-free survival (PFS) was similar in the two treatment groups (median PFS 10.4 months for Erbitux plus FOLFIRI vs. 10.2 months for bevacizumab plus FOLFIRI; HR: 0.93; 95% CI: 0.74–1.17; p=0.54).
In the group of patients with any RAS mutations (n=178), patients who received Erbitux plus FOLFIRI 1st line reached an OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab plus FOLFIRI (HR=1.09; 95% CI: 0.78–1.52; p=0.60). For patients in the Erbitux plus FOLFIRI arm, median PFS was 7.5 months compared with 10.1 months in the bevacizumab plus FOLFIRI arm (HR=1.31; 95% CI: 0.98–1.78; p=0.085), and ORR was 38.0% vs. 51.2% (p=0.097), respectively.
No new safety concerns were reported in the trial in either treatment arm and toxicity profiles were as expected and manageable for both combinations.
About Colorectal Cancer
Colorectal cancer (CRC) is the fourth most common cancer worldwide, with an estimated incidence of more than 1.2 million cases globally.4 An estimated 608,000 deaths from CRC occur worldwide each year, accounting for 8% of all cancer deaths and making it the fourth most common cause of death from cancer.4 Almost 60% of the cases occur in developed regions, and incidence and mortality rates are substantially higher in menthan in women.5 In Europe alone, an estimated 436,000 people develop CRC every year, with approximately 212,000 people dying from the disease annually.5
References
1. Heinemann V, et al. Oral presentation at the European Cancer Congress 2013, September 28. Abstract No:LBA17.
2. Heinemann V, et al. Oral presentation at the ASCO Annual Meeting 2013, June 1. Abstract No:LBA3506.
3. Modest D, et al. Oral presentation at the World Congress on Gastrointestinal Cancer 2013, July 6. Abstract No:O-0029.
4. Ferlay J, et al. Int J Cancer 2010;127(12):2893–917.
5. Ferlay J, et al. Eu J Cancer 2010;46(4):765–81.
For more information on Erbitux in colorectal and head & neck cancer, please visit: www.globalcancernews.com.
About Erbitux
Erbitux® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.
The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization in 92 countries. It has been approved for the treatment of colorectal cancer in 92 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 90 countries.
Merck licensed the right to market Erbitux outside the US and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas.
About Merck Serono
Merck Serono is the biopharmaceutical division of Merck. With headquarters in Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help patients with cancer, multiple sclerosis, infertility, endocrine and metabolic disorders as well as cardiovascular diseases. In the United States and Canada, EMD Serono operates as a separately incorporated subsidiary of Merck Serono.
Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. We have an enduring commitment to deliver novel therapies in our core focus areas of neurology, oncology, immuno-oncology and immunology.
For more information, please visit www.merckserono.com.
All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.
Merck is a leading pharmaceutical, chemical and life science company with total revenues of € 11.2 billion in 2012, a history that began in 1668, and a future shaped by approx. 38,000 employees in 66 countries. Its success is characterized by innovations from entrepreneurial employees. Merck’s operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.
SOURCE: Merck Serono
Post Views: 48
DARMSTADT, Germany/AMSTERDAM, The Netherlands I September 28, 2013 I Merck Serono, the biopharmaceutical division of Merck, today announced that the German cooperative investigator group AIO (Arbeitsgemeinschaft Internistische Onkologie) reported new data from the Phase III head-to-head clinical trial FIRE-3, which show a clinically relevant improvement from Erbitux® (cetuximab) plus FOLFIRI versus bevacizumab plus FOLFIRI as 1st line treatment in metastatic colorectal cancer (mCRC) in patients with RAS wild-type tumors.1
The new data, from a preplanned exploratory analysis, were presented at the European Cancer Congress 2013 (ECCO-ESMO-ESTRO). The analysis shows a 7.5-month increase in median overall survival (OS) in mCRC patients with RAS wild-type tumors ((n=342); defined as having no mutations in exons 2, 3 and 4 of KRAS and NRAS), receiving 1st line Erbitux plus FOLFIRI compared with patients receiving bevacizumab plus FOLFIRI (OS: 33.1 months vs. 25.6 months, respectively; hazard ratio [HR]: 0.70; p=0.011). In a post hoc analysis of the patient group with any RAS mutations (n=178), patients who received Erbitux plus FOLFIRI 1st line reached an OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab plus FOLFIRI (HR: 1.09; p=0.60).1
As previously presented at the annual meeting of the American Society of Clinical Oncology (ASCO) 2013 and at the World Congress on Gastrointestinal Cancer 2013, the primary endpoint of the trial, objective response rate based on investigators’ read in patients with KRAS exon 2 wild-type tumors, was not met.2,3 In the patient group with KRAS exon 2 wild-type tumors, an expected and balanced cross-over or continuation beyond progression with regard to subsequent biologic treatments in 2nd line therapy (either EGFR antibody or bevacizumab) was observed. Also, no major imbalances were noted with regard to chemotherapies used in 2nd line treatment. It is important to note that this result is not fully mature (57% event rate in the “intent-to-treat” KRAS exon 2 wild-type population) and will be updated in due course.2
“These new data from the Phase III study FIRE-3 show a 7.5-month increase in median overall survival to 33.1 months when using 1st line Erbitux plus FOLFIRI as compared to using bevacizumab plus FOLFIRI in metastatic colorectal cancer. Such a prolongation is a paradigm shift in mCRC treatment since the introduction of monoclonal antibodies,” said Professor Volker Heinemann from the Ludwig-Maximilians University, Munich, and FIRE-3 principal investigator. “Together with insights from other recent relevant studies, these results suggest that 1st line treatment of RAS wild-type patients should include an anti-EGFR therapy.”
“These results continue to reinforce the value of Erbitux as a 1st line treatment for metastatic colorectal cancer and show that RAS tumor status is likely to help to identify those patients who are most likely to benefit from Erbitux,” said Dr. Annalisa Jenkins, Head of Global Drug Development and Medical for Merck Serono. “Additional biomarker analyses are being conducted on data from the pivotal Erbitux studies, CRYSTAL and OPUS to help shed additional light on the role of RAS mutations in these patients.”
About the FIRE-3 study
FIRE-3 is an independent, randomized, controlled, head-to-head Phase III trial led by Ludwig-Maximilians University in Munich, Germany. Merck Serono GmbH has financially supported the study. The FIRE-3 trial is being conducted in Europe, including 752 mCRC patients of whom 592 patients had confirmed KRAS exon 2 wild-type tumors. Of these, 297 patients were randomized to Erbitux plus FOLFIRI and 295 to bevacizumab plus FOLFIRI.2 113 patients had confirmed KRAS exon 2 mutations.
Initial data from the FIRE-3 study “intent-to-treat” population were presented at ASCO 2013. The primary endpoint, objective response rate (ORR) based on investigators’ read, of the FIRE-3 trial was not met (62% for Erbitux vs. 58% for bevacizumab; odds ratio 1.18).2
Analysis of RAS tumor status1
In the population with samples available for further RAS mutation analyses (n=407;KRAS exons 3 or 4, NRAS exons 2, 3, or 4), 84% of patients have RAS wild-type tumors and 16% RAS mutant tumors (other than KRAS exon 2).
Median OS was 33.1 months in mCRC patients with RAS wild-type tumors (n=342) receiving 1st line Erbitux plus FOLFIRI compared with 25.6 months in patients receiving bevacizumab plus FOLFIRI (HR: 0.70; 95% confidence interval [CI]: 0.53–0.92; p=0.011). ORR was substantially improved (65.5% for Erbitux plus FOLFIRI vs. 59.6% for bevacizumab plus FOLFIRI p=0.157). Progression-free survival (PFS) was similar in the two treatment groups (median PFS 10.4 months for Erbitux plus FOLFIRI vs. 10.2 months for bevacizumab plus FOLFIRI; HR: 0.93; 95% CI: 0.74–1.17; p=0.54).
In the group of patients with any RAS mutations (n=178), patients who received Erbitux plus FOLFIRI 1st line reached an OS of 20.3 months vs. 20.6 months in the group that was treated with bevacizumab plus FOLFIRI (HR=1.09; 95% CI: 0.78–1.52; p=0.60). For patients in the Erbitux plus FOLFIRI arm, median PFS was 7.5 months compared with 10.1 months in the bevacizumab plus FOLFIRI arm (HR=1.31; 95% CI: 0.98–1.78; p=0.085), and ORR was 38.0% vs. 51.2% (p=0.097), respectively.
No new safety concerns were reported in the trial in either treatment arm and toxicity profiles were as expected and manageable for both combinations.
About Colorectal Cancer
Colorectal cancer (CRC) is the fourth most common cancer worldwide, with an estimated incidence of more than 1.2 million cases globally.4 An estimated 608,000 deaths from CRC occur worldwide each year, accounting for 8% of all cancer deaths and making it the fourth most common cause of death from cancer.4 Almost 60% of the cases occur in developed regions, and incidence and mortality rates are substantially higher in menthan in women.5 In Europe alone, an estimated 436,000 people develop CRC every year, with approximately 212,000 people dying from the disease annually.5
References
1. Heinemann V, et al. Oral presentation at the European Cancer Congress 2013, September 28. Abstract No:LBA17.
2. Heinemann V, et al. Oral presentation at the ASCO Annual Meeting 2013, June 1. Abstract No:LBA3506.
3. Modest D, et al. Oral presentation at the World Congress on Gastrointestinal Cancer 2013, July 6. Abstract No:O-0029.
4. Ferlay J, et al. Int J Cancer 2010;127(12):2893–917.
5. Ferlay J, et al. Eu J Cancer 2010;46(4):765–81.
For more information on Erbitux in colorectal and head & neck cancer, please visit: www.globalcancernews.com.
About Erbitux
Erbitux® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.
The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization in 92 countries. It has been approved for the treatment of colorectal cancer in 92 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 90 countries.
Merck licensed the right to market Erbitux outside the US and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas.
About Merck Serono
Merck Serono is the biopharmaceutical division of Merck. With headquarters in Darmstadt, Germany, Merck Serono offers leading brands in 150 countries to help patients with cancer, multiple sclerosis, infertility, endocrine and metabolic disorders as well as cardiovascular diseases. In the United States and Canada, EMD Serono operates as a separately incorporated subsidiary of Merck Serono.
Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. We have an enduring commitment to deliver novel therapies in our core focus areas of neurology, oncology, immuno-oncology and immunology.
For more information, please visit www.merckserono.com.
All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to www.merckgroup.com/subscribe to register online, change your selection or discontinue this service.
Merck is a leading pharmaceutical, chemical and life science company with total revenues of € 11.2 billion in 2012, a history that began in 1668, and a future shaped by approx. 38,000 employees in 66 countries. Its success is characterized by innovations from entrepreneurial employees. Merck’s operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.
SOURCE: Merck Serono
Post Views: 48
