Colorectal cancer - new drugs soon on the market

Colorectal cancer which includes cancer of the colon, rectum, anus, and appendix is, after lung cancer, a leading cause of cancer related deaths in certain parts of the world. Currently only a third to one half of patients with metastatic colorectal cancer respond to traditional chemotherapy. Latest strategy in treatment is being targeted at a specific type of receptor, the EGFR found on a cell's surface.

The epidermal growth factor receptor (EGFR) found on the surface of tumour cells, has been shown to contribute to the growth and spread of many different types of solid tumours. Activation of EGF receptors (by growth factors) can trigger the proliferation and de-differentiation that characterize cancer cells. The EGFR has also been shown to actually protect cancerous cells from the toxic effects of chemotherapy and radiotherapy, meaning that that these treatments are a lot less effective. Patients with EGFR-positive tumours have a generally poor prognosis, with a lesser chance of survival and/or an increased spread of the cancer. A new study brings some hope. Merck KgaA have unveiled promising studies of an advanced antibody, Erbitux, which targets the EGFR found on the tumour cells.

Merck announced in Chicago that data from its European colorectal cancer (BOND) study demonstrate that cetuximab, (the active substance in Erbitux) when used in combination with irinotecan, a chemotherapy drug, represents a significant advance in the treatment of patients with metastatic colorectal cancer. The treatment slows the progression of the disease by more than four months and shrinking tumors by 50 percent or more in 23 percent of patients. Half of all patients saw their disease stabilize or improve.

The average survival time for the advanced stage patients treated with the combination therapy was 8.6 months, with approximately a third of the 329 patients in the study alive after one year.

"These are very significant findings, considering how difficult advanced-stage colorectal cancer is to treat and that patients in the BOND study had already failed treatment with the standard course of chemotherapy," said Prof. David Cunningham, M.D., head of the gastrointestinal and lymphoma units at the Royal Marsden Hospital in London and Surrey, United Kingdom, and lead investigator for the BOND study. Prof. Cunningham presented results of the BOND (Bowel Oncology With Cetuximab Antibody) study at the annual meeting of the American Society of Clinical Oncology in Chicago.

"These results are likely to change the standard of care for patients with metastatic colorectal cancer whose disease is becoming worse despite conventional chemotherapy," said Prof. Cunningham. "Cetuximab gives doctors a powerful new tool and gives patients who have failed traditional chemotherapy new hope."

The BOND study was designed to compare cetuximab alone as monotherapy and in combination with irinotecan in 329 patients with metastatic colorectal cancer expressing the epidermal growth factor receptor (EGFR) who had ceased to respond to chemotherapy. Two thirds of the patients were given cetuximab and irinotecan while one third received only cetuximab. Data from the BOND study indicate that cetuximab given alone shows an overall response rate of 11 percent. When given in combination with irinotecan, a significantly higher degree of efficacy is observed, with an overall response rate of 23 percent. The study demonstrates that a combination of cetuximab and irinotecan is beneficial even when patients have ceased to respond to irinotecan.

Up to three quarters of colorectal cancer tumors express EGFR. EGFR, when expressed by tumors, usually results in aggressive disease progression, poor response to traditional therapy and poor survival. Because cetuximab blocks the EGFR, thereby inhibiting the abnormal growth of cancer cells, patients whose colorectal tumors overexpress EGFR will be most likely to benefit from cetuximab. Merck and ImClone Systems continue to conduct additional studies of Erbituxin In other EGFR-expressing tumours.

Based on the latest data and earlier studies, Merck KGaA plans to submit an application for approval of Erbitux to the European Agency for the Evaluation of Medicinal Products (EMEA) and to Swissmedic, the Swiss approval authority, this summer. Swissmedic has determined that cetuximab is suitable for an accelerated registration procedure, which means Merck could bring the cancer drug to market in Switzerland as soon as late 2003. Approval in the EU could follow in 2004. The company expects to have Erbitux available in more than 20 countries by the end of 2005. Merck is currently conducting additional clinical trials in Japan, which will be needed to support a submission in that market.

Merck KGaA remains focused on the regulatory submission of cetuximab so that patients most likely to benefit will have access to cetuximab as soon as possible.


September 2003