ATLANTA, GA--6 Jun--PRNewswire-AsiaNet/InfoQuest
Abstracts: 3085, 3509, 3535, 3549, 3555, 3556, 5537, 7109
Location: 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) 2006, Atlanta, Georgia
Merck KGaA releases wealth of new Erbitux(R) (cetuximab) data at ASCO Annual Meeting
Data presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) from a clinical trial involving 1,147 patients whose metastatic colorectal cancer (mCRC) has failed prior irinotecan-based treatment, show that targeted cancer therapy, Erbitux(R) (cetuximab) plus irinotecan, demonstrated a median survival of 9.2 months.(1) These results clearly confirm in more than 1,000 patients the efficacy and safety of Erbitux plus irinotecan in pre-treated patients and provide further evidence that
Erbitux is delivering on its promise.
"We are extremely encouraged by the results reported here," said Professor Hansjochen Wilke, Kliniken Essen Mitte, Essen, Germany, lead investigator of the study. "Treating patients whose disease is no longer responding to standard chemotherapies is a challenge for physicians. Erbitux plus irinotecan is proving a highly effective treatment for these patients and has been established as a standard of care in patients failing prior irinotecan-based therapy."
The study, known as MABEL[a
], was conducted in 197 centers across eight European countries, and evaluated progression-free survival rates in patients with mCRC whose disease had failed prior irinotecan-based therapy. Patients were treated with Erbitux combined with irinotecan. The progression-free survival rate was 61 percent at 12 weeks and 34 percent at 24 weeks, clearly confirming the efficacy of this treatment option seen in previous studies.(1) In addition, preliminary findings from a clinical trial of Erbitux and chemotherapy in previously untreated patients with mCRC were reported by Alan Venook, M.D., Professor of Medicine, University of California, San Francisco on behalf of the CALGB[b
]. Patients with untreated mCRC were enrolled in the study and randomized to receive either chemotherapy (randomized between irinotecan/5FU/LV [FOLFIRI
] or oxaliplatin/ 5FU/LV [FOLFOX
]) or chemotherapy plus Erbitux. The study, CALGB 80203, was initiated in 2004 and was originally planned to recruit approximately 2,200 patients. Enrollment was closed after accrual of 238 patients due to an evolving standard of care in the first-line treatment of mCRC. The primary endpoint of the study was overall survival and secondary endpoints included response rate, progression-free survival and toxicity. As the study was closed prematurely, it is not powered for statistical analysis of progression-free and overall survival, and conclusions are impossible to reach. However, response rate among patients treated with the combination of Erbitux and chemotherapy was significantly higher than that for patients treated with chemotherapy alone (52 percent versus 38 percent,
respectively, p=0.029).(2)
Investigation of an alternative dosing schedule for Erbitux
Further data presented at the ASCO Annual Meeting show that administration of Erbitux every second week (rather than the current standard weekly dosing) could be an alternative dosing schedule for patients.(3) It could be demonstrated that Erbitux administered at 500 mg/msquared every second week provided similar pharmacokinetic results compared to the current weekly standard dosing regimen of 250 mg/msquared. This result is of great importance, because it provides the patients and oncologists with flexible dosing convenience.
Erbitux phase III studies will continue as planned
Also presented at the conference are early results from several international phase III clinical trials involving over 4,000 patients revealing that the independent Data Safety Monitoring Boards (DSMB) recommended that the Erbitux trials could continue.(4-7) These phase III clinical trials are in challenging cancer types, including mCRC, squamous cell carcinoma of the head and neck (SCCHN) and non-small-cell lung cancer (NSCLC).(4-7)
Two large phase III studies are being conducted in mCRC: EPIC[c
],(4) (examining the use of Erbitux in combination with irinotecan after failure of oxaliplatin-based chemotherapy in 1,301 patients) and CRYSTAL[d
],(5) (investigating Erbitux with irinotecan in 1,221 patients as a first-line treatment). These results allow for the continuation of the phase III studies investigating and building on the already exceptional phase II studies, that consistently showed high response rates up to 81 percent in the first-line treatment of mCRC. This has allowed nearly one in four patients to have their previously inoperable metastases that have spread to their liver removed by surgery.(8,9,10) So far the only approach in mCRC with the hope for cure is surgical removal of metastases mainly found in the liver.(11,12)
The phase III EXTREME trial[e
],(6) is investigating the first-line treatment of Erbitux in combination with chemotherapy (cisplatin plus 5-FU or carboplatin plus 5-FU) in 442 patients with recurrent and/or metastatic SCCHN.
The phase III FLEX study[f
],(7) is examining the survival benefits of first-line use of Erbitux with chemotherapy (cisplatin and vinorelbine) versus chemotherapy alone in 1,125 patients with advanced NSCLC.
"Data on Erbitux presented at this year's ASCO Annual Meeting reinforce the outstanding efficacy in first and later lines of therapy in patients with metastatic colorectal cancer failing prior chemotherapy," said Dr. Wolfgang Wein, Senior Vice President, Global Oncology Commercialization at Merck KGaA. "We are also very encouraged by the new data showing that Erbitux can be
administered in an every second week schedule."
Notes for Editors
About ERBITUX
ERBITUX(R) 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 five percent of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.
Erbitux has already obtained market authorization to treat colorectal cancer in 53 countries: Switzerland, the US, Mexico, Argentina, Chile, Iceland, Norway, the European Union, Peru, Australia, Croatia, Israel, Bulgaria, Panama, Guatemala, Colombia, Singapore, Hong Kong, South Korea, Canada, Ecuador, Malaysia, the Philippines, Taiwan, China, India, Lebanon, Venezuela and
Nicaragua for the use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. In the US, Argentina, Chile, Mexico, Peru, Singapore, Australia, Panama, Colombia, Guatemala, Hong Kong, Canada, Ecuador, the Philippines, Lebanon, Venezuela and Nicaragua Erbitux is also approved for single-agent use.
In addition Erbitux in combination with radiotherapy has been approved for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in Switzerland, Argentina, Colombia, the US, the European Union, Norway, Iceland and the Philippines. In Argentina, the US and the Philippines,
Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.
About Merck KGaA
Merck KGaA, Darmstadt, Germany, licensed the right to market Erbitux outside the US and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, Merck KGaA has co-exclusive marketing rights with ImClone Systems.
Merck KGaA has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck KGaA has also acquired the rights for the cancer treatment UFT(R) (tegafur-uracil) -- an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.
Merck KGaA is also investigating among other cancer treatments the use of Stimuvax(R) (formerly referred to as BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing
rights from Biomira Inc. of Edmonton, Alberta, Canada, with the exception of Canada where the companies will share rights.
References:
1. Wilke H et al. Poster presentation at ASCO, Atlanta, Georgia,
2006; ID number 3549
2. Venook A et al. presentation at ASCO, Atlanta, Georgia, 2006;
ID number 3509
3. Tabernero J et al. Poster presentation at ASCO, Atlanta,
Georgia, 2006; ID number 3085
4. Abubakr Y et al. Poster presentation at ASCO, Atlanta, Georgia,
2006: ID number 3556
5. Lang I et al. Poster presentation at ASCO, Atlanta, Georgia,
2006: ID number 3555
6. Vermorken J et al. Poster presentation at ASCO, Atlanta, Georgia,
2006; ID number 5537
7. Von Pawel J et al. Poster presentation at ASCO, Atlanta, Georgia,
2006; ID number 7109
8. Diaz Rubio E et al. Presented at ASCO, Orlando, Florida, 2005:
abstr 3535
9. Folprecht G et al. Cetuximab and irinotecan/5-fluorouracil/folinic
acid is a safe combination for the first-line treatment of patients
with epidermal growth factor receptor expressing metastatic
colorectal carcinoma. Ann Oncol 2006; 17: 450-456
10. Peeters M et al. Eur J Cancer 2005; Supplement 3: Abstract 664
11. Macdonald JS. Adjuvant Therapy of Colon Cancer. CA Cancer J Clin
1999; 49 (4), 202-219.
12. Mineo TC et al. Long term results after resection of simultaneous
and sequential lung and liver metastases from colorectal carcinoma.
J Am Coll Surg 2003; 197: 386-391.
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Merck is a global pharmaceutical and chemical company with sales of EUR 5.9 billion in 2005, a history that began in 1668, and a future shaped by 29,133 employees in 54 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 a 73% interest and free shareholders own the remaining 27%. The former U.S. subsidiary, Merck & Co., has been completely independent of the Merck Group since 1917.
[a
] Monoclonal Antibody Erbitux in a European Pre-License Study
[b
] The Cancer and Leukemia Group B
[c
] European Prospective Investigation of Cancer
[d
] Cetuximab combined with iRinotecan in first-line therapY
for metaSTatic colorectAL cancer
[e
] ErbituX in first-line Treatment of REcurrent or MEtastatic
head & neck cancer
[f
] First-line in Lung cancer with ErbituX
SOURCE: Merck KGaA
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