The study data on the monoclonal antibody Erbitux® (cetuximab) impressively demonstrate the consistent efficacy and versatility of this targeted cancer therapy. When used in combination with current standard irinotecan-based chemotherapy in the first-line treatment of patients with metastatic colorectal cancer, Erbitux® significantly increased progression-free survival, response and resection rates. The prospects for removing the liver metastases surgically improve considerably – as does the chance of cure. The number of patients in whom shrinkage of metastases was large enough to allow a complete resection was three times higher in the Erbitux® group than in the control arm. These encouraging results of the so-called CRYSTAL study underscore the importance of Erbitux® as a new option in the first-line treatment of metastatic colorectal cancer. In addition, a clinical Phase II trial (BALI-1) has been started to study the use of Erbitux® to treat breast cancer. A Phase III trial in gastric cancer (EXPAND) is in preparation.
In the treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck, a breakthrough was achieved with Erbitux®. A Phase III study (EXTREME) showed that the patients who received Erbitux® in combination with either cisplatin- or carboplatin-based therapy had a significantly longer survival, an almost doubling of the time to tumor progression and a significantly higher response rate compared with patients treated with platinum-based therapy alone. This is the first time in 25 years that a survival benefit has been demonstrated in this group of patients in a randomized Phase III trial.
Merck is also conducting promising clinical trials of Erbitux ® in lung cancer, a major indication.
A Phase III study (FLEX) on the use of Erbitux® combined with vinorelbine plus cisplatin met the primary endpoint of increasing overall survival compared with chemotherapy alone in patients with advanced non-small-cell lung cancer (NSCLC).
Development of further cancer drugs improves prospects for treatment
A novel combination regimen based on the cancer drug UFT® (tegafur-uracil), an oral form of the standard chemotherapy 5-fluorouracil (5-FU) plus leucovorin (LV) administered by infusion, demonstrated a high response rate of 66% in the first-line treatment of advanced metastatic colorectal cancer. This confirmed that UFT® is an effective alternative to 5-FU i.v. in this indication. The further development of the humanized monoclonal antibody matuzumab for the treatment of metastatic colorectal cancer was terminated. A Phase II study on the efficacy of matuzumab in combination with irinotecan failed to meet the predefined endpoint. In addition, Merck Serono returned the rights to develop and market zanolimumab (HuMax-CD4) for the treatment of T-cell lymphoma to Genmab.
Important results were delivered by a randomized Phase II study with Stimuvax® (BLP25 liposome vaccine) – a therapeutic cancer vaccine that Merck Serono is developing to treat non-small-cell lung cancer. Novel therapeutic vaccines can help the body’s immune system to identify tumor cells and to destroy them without attacking healthy cells. Updated survival data in the subgroup of patients with locoregional disease show that in the arm that received the cancer vaccine in combination with the best supportive treatment, after three years more than twice as many patients were still alive compared to the group that received best supportive treatment, but not the cancer vaccine. Based on these positive results, Stimuvax® is now being studied in Phase III trials. The START trial is the first Phase III study to investigate a vaccine in inoperable stage III non-small-cell lung cancer.
With cilengitide, Merck Serono is developing a highly effective drug to treat glioblastoma – a particularly aggressive form of brain tumor. This integrin inhibitor suppresses the new formation of blood vessels (angiogenesis) and cuts the tumor off from the blood supply. In addition, cilengitide acts directly on tumor cells. The clinical activity of cilengitide in newly diagnosed glioblastoma patients was studied in combination therapy with radiotherapy and a chemotherapeutic agent. In nearly 70% of patients, the tumor had not grown further after six months, median progression-free survival was eight months. These results point to the potential of cilengitide to considerably improve the outcome of patients with this aggressive type of brain cancer, without adding major toxicities.
