* New data from CRYSTAL study demonstrate overall survival improvement with Erbitux – the first time this was ever achieved with an EGFR-inhibitor
* Additionally, results of a meta-analysis demonstrate clear survival and tumor response benefits of Erbitux in this setting with FOLFOX or FOLFIRI
Berlin, Darmstadt, Germany | September 23, 2009 | Merck KGaA, Darmstadt, Germany, today announced that Erbitux® (cetuximab) demonstrated a significant improvement in overall survival (OS) when added to standard 1st-line chemotherapy for metastatic colorectal cancer (mCRC) patients with KRAS wild-type tumors. This is the first time an OS benefit has been demonstrated with an epidermal growth factor receptor (EGFR)-inhibitor in this disease setting. These results from the pivotal CRYSTAL(a) trial were presented at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO) held in Berlin, Germany this week.
“Overall survival is a critically important outcome in metastatic colorectal cancer so it is extremely rewarding to achieve this result for the first time with an EGFR targeted therapy added to a standard chemotherapy,” commented Professor Eric Van Cutsem, principal investigator of the CRYSTAL study and Professor of Medicine and Digestive Oncology from the University Hospital Gasthuisberg in Leuven, Belgium. “We are excited to be the first to demonstrate this with Erbitux – a result that has the potential to significantly extend the lives of patients with KRAS wild-type tumors.”
CRYSTAL overall survival data
In patients with KRAS wild-type tumors receiving Erbitux plus FOLFIRI:
· Median OS was 23.5 months compared to 20.0 months in those receiving chemotherapy alone (hazard ratio [HR] 0.796; p=0.0094)
· The risk of disease progression was reduced by 30% (HR 0.696; p=0.0012)
· The likelihood of achieving a tumor response doubled overall (RR 57.3% vs. 39.7%; p<0.0001)(1)
OPUS overall survival data
The unparalleled CRYSTAL results are further supported by new data from the OPUS study, also presented today, demonstrating:
· Median OS in patients with KRAS wild-type tumors of 22.8 months was seen in the Erbitux plus chemotherapy arm compared with 18.5 months in the chemotherapy-alone arm (HR 0.855; p=0.3854).(2)
These OS data were presented alongside a meta-analysis of the CRYSTAL and OPUS(b) studies which demonstrated improvements in several critical outcomes for mCRC patients with KRAS wild-type tumors treated with Erbitux plus chemotherapy.
CRYSTAL/OPUS meta-analysis
The meta-analysis was designed to evaluate OS, progression-free survival (PFS) and response rate (RR) in the combined CRYSTAL and OPUS populations of patients with KRAS wild-type tumors (n=845). The analysis showed that for the combined population:
· The risk of death was reduced by 19% (HR 0.81; p=0.0062) for patients receiving Erbitux plus chemotherapy compared with those receiving chemotherapy alone
· The risk of disease progression was reduced by 34% (HR 0.66; p<0.0001) for patients receiving Erbitux plus chemotherapy compared with those receiving chemotherapy alone
· The likelihood of achieving a response in patients receiving combination treatment increased more than two-fold compared to those receiving only chemotherapy (OR 2.16; p<0.0001)(1)
Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono division, concluded: “These results from the meta-analysis show that Erbitux is the first and only targeted therapy to achieve a significant survival benefit in combination with the standard chemotherapy regimens FOLFOX and FOLFIRI in 1st-line mCRC patients with KRAS wild-type tumors.”
Colorectal cancer
More than 370,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths.(3) Approximately 25% of patients present with metastatic disease.(4) Five-year survival rates for patients with mCRC are as low as 5%.(5)
aCRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer
bOPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC
References
1. Van Cutsem E, et al. ECCO/ESMO Congress 2009. Abstract No: 6077.
2. Bokemeyer C, et al. ECCO/ESMO Congress 2009. Abstract No: 6079.
3. Parkin DM, et al. CA Cancer J Clin 2005;55:72–108.
4. Cunningham D, et al. Eur J Cancer 1993;29A(15):2077–2079.
5. Macdonald JS. CA Cancer J Clin 1999;49(4):202–219.
For more information on Erbitux in colorectal, head & neck and non-small cell lung 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 77 countries. It has been approved for the treatment of colorectal cancer in 77 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 72 countries:
· December 2003 (Switzerland), February 2004 (USA), June 2004 (EU) and followed by other countries: for use in combination with irinotecan in patients with EGFR-expressing mCRC (metastatic colorectal cancer) who have failed prior irinotecan therapy. In addition, Erbitux is also approved for single-agent use in further countries.
· April 2006 (EU) and followed by other countries: for use in combination with radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). In further countries, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.
· July 2008 (EU): license was updated for the treatment of patients with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type mCRC in combination with chemotherapy and as a single agent in patients who have failed oxaliplatin-and irinotecan-based therapy and who are intolerant to irinotecan.
· July 2008 (Japan): for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy
· In November 2008 (EU): license was updated for the use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN
Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone Systems, 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, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT® (tegafur-uracil) – an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.
Merck is also investigating among other cancer treatments the use of Stimuvax® (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 Oncothyreon Inc., Seattle, Washington, USA.
In addition, Merck is developing cilengitide, which is the first in a new class of investigational anti-cancer therapies called integrin inhibitors to reach Phase III of development; it is currently being investigated for the treatment of glioblastoma, SCCHN and NSCLC. Integrin inhibitors are thought to work by targeting the tumor and its vasculature.
Merck is a global pharmaceutical and chemical company with total revenues of € 7.6 billion in 2008, a history that began in 1668, and a future shaped by approximately 33,000 employees in 60 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 KGaA
