Merck Serono, a division of Merck KGaA, Darmstadt, Germany announced that long-term follow-up data of a randomized phase-II study of two cilengitide doses in recurrent glioblastoma were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The data showed that treatment of 15 patients with the investigational integrin-inhibitor for more than six months and for up to 4.5 years did not result in any treatment-related severe adverse events (Grade 3/4). In addition, 37 per cent of patients who received the higher dose of cilengitide (2000 mg) were still alive after one year and 22 per cent after two years. The current prognosis of patients with recurrent glioblastoma is poor with median overall survival (OS) between four to seven months and one year survival rates of approximately 20 per cent.

Treatment-related adverse events (AEs) usually occurred within the first six months of receiving cilengitide and the most common (>1 patient) was fatigue (n=3). The most common non-treatment-related grade 3/4 serious AE was convulsion (n=2).

“The prognosis for patients with recurrent glioblastoma is extremely poor and additional treatment options have been desperately needed for some time,” said Dr Karen Fink, Baylor University Medical Center, Dallas. “We are excited about the results of this study, in that patients were able to receive cilengitide beyond six months with no treatment-related severe adverse events. Moreover, 10 per cent of patients were still alive after four years.”

The randomized phase-II study also supports the phase-I study finding of activity with cilengitide monotherapy4 and indicates that cilengitide efficacy is dose-dependent with OS and long-term survival rates consistently higher for the 2,000 mg treatment group compared to the 500 mg group during more than four years of follow-up.

“These positive long-term data once again support our ongoing phase-III study program of cilengitide in patients with this devastating disease. We believe that cilengitide may play a valuable part in the future care of glioblastoma patients,” said Dr Wolfgang Wein, executive vice president, Oncology,
Cilengitide is currently being developed by Merck Serono. Cilengitide is the first in a new class of investigational anti-cancer therapies called integrin inhibitors in 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 tumour and its blood supply.

Integrins are cell surface receptors that are improperly regulated in many cancer types. This lack of regulation enables them to enhance tumour growth, survival and invasiveness. Integrins are fundamental in the process of angiogenesis (blood vessel growth) – a process that is essential for tumours as it enables them to grow past a finite size.

In addition to the Merck Serono-sponsored studies, the US National Cancer Institute (NCI) is sponsoring a number of clinical trials under a Cooperative Research and Development Agreement (CRADA) with Merck Serono for the development of cilengitide. In the United States and Canada, cilengitide is being developed by EMD Serono, an affiliate of Merck KgaA.