The results of numerous studies involving the monoclonal antibody Erbitux® (cetuximab) impressively demonstrate the consistent efficacy and versatility of this targeted cancer therapy. In metastatic colorectal cancer, for example, it is now possible to use the KRAS gene as a biomarker to identify those patients who are most likely to respond to treatment with Erbitux®, namely those with KRAS wild-type tumors.
The results of the Phase III CRYSTAL trial underline the value of Erbitux® as a new standard in first-line treatment of metastatic colorectal cancer. In this large randomized trial, 60% of all patients with KRAS wild-type tumors experienced significant tumor shrinkage when treated with Erbitux® in combination with chemotherapy – clearly exceeding the results achieved with chemotherapy alone. The ability of Erbitux® to shrink the tumor translated into a substantially decreased risk of tumor progression and a trend towards prolonged survival for all patients with KRAS wild-type tumors. Furthermore, effective tumor shrinkage might allow complete surgical resection of liver metastases, thereby enhancing the chance of a potential cure. A further randomized Phase II study (CELIM) investigated the efficacy of Erbitux® in combination with standard chemotherapy in patients with initially inoperable liver metastases. Tumor shrinkage was experienced by 79% of patients with KRAS wild-type tumors, and 43% of these patients underwent surgery. A complete surgical removal of the tumor was achieved in 34% – a chance for these patients to be cured. These data are among the best ever achieved for complete surgical removal of liver metastases in metastatic colorectal cancer.
Erbitux® in lung and gastric cancer
A Phase III clinical trial (FLEX) proved that in first-line treatment in combination with a platinum-based chemotherapy, Erbitux® can significantly prolong median overall survival of patients with non-small-cell lung cancer (NSCLC) across all histological patient subgroups. This effect was more pronounced in FLEX patients treated with Erbitux® who developed early acne-like rash, resulting in median overall survival of 15 months. Lung cancer is one of the leading causes of cancer death worldwide: Among men, it claims more lives – around 975,000 per year – than any other form of cancer. Among women, it is responsible for 376,000 deaths each year, second to breast cancer.
A further Phase III clinical trial (EXPAND) was started in the third quarter of 2008 to investigate the efficacy of Erbitux® in combination with chemotherapy as a new option in first-line treatment of gastric cancer. Every year, nearly 930,000 people are diagnosed with gastric cancer and around 700,000 die from it.
Expanding treatment possibilities in oncology
Two further compounds, Stimuvax® and cilengitide, are currently in Phase III development. Stimuvax® (BLP25 liposome vaccine) is an investigational therapeutic cancer vaccine designed to induce an immune response to cancer cells that express MUC1, a protein antigen over-expressed in many common cancers including lung, breast and colorectal cancer. Stimuvax® is currently in a Phase III study involving patients with non-small cell lung cancer (NSCLC). It is the first cancer vaccine in unresectable locally advanced NSCLC to enter Phase III clinical trial testing (START). The results of a randomized Phase II study found that after three years, almost twice as many patients with unresectable advanced NSCLC receiving Stimuvax® were still alive compared to patients in the control group.
Merck Serono is currently evaluating the investigational integrin inhibitor cilengitide in glioblastoma – the most aggressive form of brain tumor – and in head and neck cancer. Cilengitide is thought to suppress the new formation of blood vessels (angiogenesis) and cut off the tumor from the blood supply. In addition, it is believed to target tumor cells directly. Following Phase II data, cilengitide is now being studied in a global Phase III trial (CENTRIC) to evaluate its efficacy in patients with newly diagnosed glioblastoma. All patients enrolled in the study are carriers of a specific chemical modification in a certain section of their DNA (methylated MGMT promoter). A further Phase II trial (ADVANTAGE) is evaluating the novel combination of cilengitide and Erbitux® in squamous cell carcinoma of the head and neck. In addition, we entered into a worldwide alliance with Lpath, Inc. of the United States to develop and commercialize sonepcizumab (ASONEP™), a Phase I monoclonal antibody currently being evaluated for the treatment of various cancer types.