Roche and Genentech temporarily suspend recruitment to colon cancer trial

Roche and Genentech have temporarily suspended recruitment of patients for their AVANT trial; a three-arm global study assessing the effectiveness of Avastin, Genentech's US Food and Drug Administration (FDA) approved inhibitor of angiogenesis - the process by which new blood vessels develop and carry vital nutrients to a tumour - as an adjuvant therapy in the treatment of advanced colon cancer.

The trial was adding Avastin to the chemotherapy regimens Folfox-4 or Xelox to see if it prolonged disease-free survival in patients who had no evidence of macroscopic disease after curative surgery, and to determine its safety profile in these settings. The review has been recommended by the AVANT independent Data Safety Monitoring Board (DSMB) following a safety concern in Arm C of the trial, Xelox + Avastin, where of the seven deaths (1% of the trial population) that have occurred four were 'sudden' and three of the four were in 'younger patients'.

Arm A of the trial, Folfox-4 has seen four deaths (0.6%) and Arm B, Folfox-4 + Avastin, has seen three (0.4%).

The fast recruitment in the trial was also seen as a cause for concern as it 'could prevent adequate and timely intervention'. Since it began recruitment in December 2004 almost two-thirds of the target number of 3,450 patients have been enrolled and more than 250 patients were enrolled in January 2006 alone.

The suspension is supported by the companies and will enable the DSMB to undertake a review of 60-day safety data and look at all adverse events in the study, including gastrointestinal perforations, which were observed in previous studies of Avastin plus chemotherapy and that have been observed in the AVANT study at a rate of 1%. Patients already enrolled in the trial will continue treatment as per the study protocol, and all other ongoing Roche studies in the oncology area, including with Avastin, will continue as planned. Roche stock fell 2% while Genentech lost 1.7% following the announcement.

Following indications that its mechanism may be relevant in a number of malignant tumours, Roche and Genentech are also investigating Avastin in breast, lung, pancreatic cancer, ovarian cancer and renal cell carcinoma. Approximately 15,000 patients are expected to be enrolled into clinical trials over the next years worldwide.

Avastin was approved in February 2004 in the US and in January 2005 in the EU for the treatment of patients with previously untreated metastatic colorectal cancer, for which it is generally well-tolerated and has a sound safety profile. It has been used in over 54,000 patients worldwide.