In First Line Treatment Of Metastatic Colorectal Cancer Erbitux Demonstrates Consistent Efficacy

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Cancer / Oncology
Article Date: 03 Jul 2007 - 1:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

The first European presentation of key Erbitux® (cetuximab) data at the 9th World Congress of Gastrointestinal Cancers (WCGIC) reinforces the consistent efficacy of Erbitux in the first-line treatment of metastatic colorectal cancer (mCRC). The key Erbitux studies presented - involving more than 70 centres across Europe - represent best practice in clinical trials management and collaboration.

Two key studies presented at the meeting, validate the role of Erbitux as an effective first-line treatment in mCRC patients, when used in conjunction with two different types of chemotherapy treatment. The CRYSTALa trial, a phase III study of Erbitux plus FOLFIRI (irinotecan-based therapy) compared with FOLFIRI alone, met the primary endpoint of significantly increasing median duration of progression-free survival in patients with previously untreated mCRC. This randomized, controlled trial studied almost 1,200 patients and demonstrated a 15% reduction (hazard ratio: 0.085) in the risk of metastatic colorectal cancer growing or spreading compared to the control arm, which was statistically significant (p=0.0479). In addition, one year after trial therapy initiation, 34% of patients in the Erbitux arm had not progressed vs 23% of patients in the control arm.

The study also achieved its secondary endpoint of significantly increasing response rate (tumor shrinkage by 50% or more) (47% in the Erbitux plus FOLFIRI group compared to 39% in the FOLFIRI alone group). Furthermore, in a subgroup analysis of patients who had liver limited disease (patients who had liver metastases only), the positive effect of the addition of Erbitux was even more pronounced, resulting in a PFS of 11.4 months with Erbitux vs. 9.2 months in the control arm and a 36% reduction in the risk of metastatic colorectal cancer growing or spreading. The number of complete resections of the metastases in the subgroup who had liver metastases only was more than double with Erbitux plus FOLFIRI vs. control arm (9.8% versus 4.5%). The number of complete resections in the overall population was three times higher in the Erbitux plus FOLFIRI arm.

"These results indicate that we have a new first-line treatment option for metastatic colorectal cancer," said Eric Van Cutsem, MD, PhD, a professor at University Hospital Gasthuisberg in Leuven, Belgium, and lead author of the study. "These findings are remarkable because they point towards the potential for this combination to provide a cure for those patients who were able to undergo a complete resection."

The CRYSTAL results were supported by the findings of the OPUSb study. Erbitux plus FOLFOX (oxaliplatin-based therapy) was compared with FOLFOX alone to measure overall response rate (tumor shrinkage by 50% or more). Response rate was found to be 46% in the Erbitux arm compared with 36% in the oxaliplatin-only arm. The safety profile of Erbitux in combination with chemotherapy was manageable and consistent with the current safety information.

Commenting on the studies, Carsten Bokemeyer, MD, PhD and lead author for the OPUS study from the University Hospital Hamburg, Germany, says: "Overall, these first-line studies demonstrate that, when added to current standard chemotherapy, Erbitux significantly increases response and resection rates, which in turn, significantly increases the chance of cure for mCRC patients."

As well as first-line use, a number of studies presented at WCGIC reinforce the versatility of Erbitux in treating a broad range of patients with mCRC. Data from the phase III EPICc study, which compared Erbitux plus irinotecan with irinotecan alone in mCRC patients who had failed first-line treatment with oxaliplatin-based chemotherapy, showed that progression-free survival, response rate and health-related quality of life was significantly improved in the Erbitux arm. A new retrospective European study (Bouchahda et al) on the use of Erbitux in elderly patients with extensively pre-treated mCRC demonstrated that the combination of Erbitux with irinotecan-based therapy resulted in good activity and acceptable tolerability comparable to that of the non-elderly population.

Commenting on the data for an important subgroup of the CRYSTAL trial, which had liver limited disease, Dr Wolfgang Wein, Senior Executive Vice President, Oncology, Merck Serono - a division of Merck KGaA, Darmstadt, Germany said "We are delighted with the results presented at WCGIC. Besides the significant outcomes for the overall population in the CRYSTAL trial we were able to define the patients with the greatest benefit. In patients with metastases limited to the liver 10% of patients had a complete resection of the tumor, which means hope for cure. This was possible because Erbitux significantly increased the tumor response rate".

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.1 Approximately 25% of patients present with metastatic disease.2 Five-year survival rates for patients with mCRC are as low as 5%.3

CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer

OPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC

EPIC: European Prospective Investigation of Cancer

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 66 countries. It has been approved for the treatment of colorectal cancer in 65 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Israel, Kazakhstan, Lebanon, Malaysia, Mexico, Montenegro, New Zealand, Nicaragua, Norway, Panama, Peru, the Philippines, Russia, Serbia, Singapore, South Korea, Switzerland, Taiwan, Thailand, Ukraine, the US, and Venezuela for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. Erbitux is also approved for single-agent use in: Argentina, Australia, Canada, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Hong Kong, Lebanon, Mexico, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela.

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 57 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Israel, Kazakhstan, Malaysia, Mexico, Montenegro, Nicaragua, Norway, Panama, the Philippines, Russia, Serbia, Singapore, Switzerland, Taiwan, Ukraine, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Mexico, Nicaragua, the Philippines, Russia, and the US, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.

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® (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® (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 share rights.

References:

1. Parkin DM et al. CA Cancer J Clin 2005; 55: 72-108.
2. GLOBOCAN. http://www-dep.iarc.fr/
3. Argiris A et al. Cancer 2004; 101: 2222-2229.


http://www.erbitux.com