Following consultation with the US Food and Drug Administration, biotechnology giant Genentech says it has terminated recruitment of patients into a Phase II study of its Avastin (bevacizumab) in advanced ovarian cancer, following reports of five gastrointestinal perforations in the first 44 participants enrolled out of the proposed 53.
Commenting on this development, Hal Barron, the group’s senior vice president of development and chief medical officer, explained: "GI perforations are a known possible adverse event with Avastin; however, we chose to discontinue enrollment in this Phase II study due to the observation of a higher rate seen in this study than in other trials of Avastin in ovarian cancer or other tumour types.”
In spite of the setback, the firm is sticking to its original plan to study Avastin in earlier-stage ovarian cancer, based on the activity seen to date and the significant unmet medical need in this patient population. According to Mr Barron, the results should not affect plans to assess the drug’s safety and efficacy other tumour types.
Speaking on the difficulties in determining the degree of risk the drug presents for this adverse event, Mr Barron noted: "The limited overall number of GI perforations seen in this study prevent us from ascertaining definitive risk factors for this adverse event. Patients enrolled in this study had more advanced disease, which typically involves the bowel, and had received more prior chemotherapy than in previous clinical trials of Avastin in ovarian cancer.”
Avastin, a therapeutic antibody designed to inhibit vascular endothelial growth factor, has a well-established safety profile. The drug was first approved for the treatment of colorectal cancer in the USA [[27/02/04a]] and subsequently in Europe [[14/01/05b]], and has already shown promise as a therapy for non-small cell lung cancer [] and breast cancer. The agent racked up 2004 sales of some $555 million dollars for Genentech [[11/01/05d]], and is widely expected to become a blockbuster earner for the company and its development partner and majority-owner Roche [[14/07/04c]].