Roche announced that a US phase III trial of Avastin (bevacizumab) in combination with gemcitabine chemotherapy as first-line treatment for advanced pancreatic cancer did not meet its primary endpoint of overall survival.
The decision to stop the trial was taken following a recommendation of an independent data monitoring board based on an interim analysis indicating that it is very unlikely that significant differences in overall survival will be shown between treatment arms as the data mature. The study was not stopped due to safety events and no new safety concerns related to Avastin were observed in this trial. The existing filings and approvals in colorectal, lung and breast cancer are not affected.
Pancreatic cancer is recognized as one of the most aggressive and most difficult-to-treat forms of cancer.
"Pancreatic cancer has a very high mortality and a short life expectancy and treatments that may improve survival are desperately needed. We will be further evaluating the data to understand potential reasons why this combination therapy did not lead to a clinical benefit in this trial", said Eduard Holdener, Head of Global Development at Roche. "In addition, we will continue with the large Avastin development programme and investigate the medicine in a broad range of cancers including another study in pancreatic cancer where Avastin is added to a standard regimen and Tarceva. It is important to note that Avastin is the first and only anti-angiogenic therapy with demonstrated significant survival benefits in the three most common cancer types: colorectal, lung and breast cancer."
The US phase III trial was sponsored by the NCI (National Cancer Institute) and NCI collaborators and investigators working on other Avastin pancreatic cancer trials will be notified of this development.
Roche and Genentech are pursuing a comprehensive clinical programme investigating the use of Avastin in 25 cancer types (including colorectal, breast, lung, pancreatic cancer, ovarian cancer, renal cell carcinoma, prostate cancer and others) across different settings. The trial programme also involves less prevalent and other difficult-to-treat cancers. The total development project is expected to include over 40,000 patients worldwide.
In Europe, Avastin was approved in early 2005 and in the US in 2004 for first-line treatment of patients with advanced colorectal cancer. Avastin was filed in April this year in the US for the most common form of lung cancer. The first filing for Avastin in Japan has been submitted in April 2006 for the treatment of advanced colorectal cancer. Most recently on May 26, 2006 Avastin was filed in the US for the treatment of women with advanced breast cancer.
This randomized, controlled, multi-center trial of 602 advanced pancreatic cancer patients was sponsored by the National Cancer Institute (NCI), and conducted by a network of researchers led by the Cancer and Leukaemia Group B (CALGB). Patients enrolled were randomized to receive treatment with gemcitabine with or without Avastin as a first-line therapy. Patients who had received prior chemotherapy for metastatic disease, adjuvant chemotherapy within the previous four weeks or any prior treatment with gemcitabine or Avastin in the adjuvant or metastatic setting were excluded from enrolling in the study. Patients with a prior history of bleeding events and those who experienced a surgical procedure, open biopsy, or significant traumatic injury during the prior 28 days were also excluded from the study. The statistical plan included pre-specified futility analyses that were conducted and reviewed by an independent Data Monitoring Board.
AVITA (BO17706) is a Roche-sponsored randomised, double blind, placebo controlled study of Gemcitabine and Tarceva+/- Avastin in patients with metastatic pancreatic cancer. The first patient was enrolled on 18 July 2005 and recruitment is expected to end before the end of 2006.
Based on an unblinded efficacy and safety analysis conducted in April 2006, the independent Data Safety Monitoring Board (DSMB) recommended that the study continues as planned.
Avastin is the first treatment that inhibits angiogenesis - the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin targets a naturally occurring protein called VEGF (Vascular Endothelial Growth Factor), a key mediator of angiogenesis, thus choking off the blood supply that is essential for the growth of the tumour and its spread throughout the body (metastasis).