Avastin Study Patients Develop Congestive Heart Failure, Enrollment SuspendedSep 28, 2009 | Parker Waichman LLP
Enrollment in an Avastin clinical trial has been halted after six patients developed clinical congestive heart failure. According to a report in The Wall Street Journal, the trial protocol requires that enrollment stop if six or more cases of clinical congestive heart failure are seen in the first 200 patients.
Avastin was the first approved therapy designed to inhibit angiogenesis, the process by which new blood vessels develop and carry vital nutrients to a tumor. Avastin was approved by the Food & Drug Administration (FDA) in 2004 to treat metastatic colon cancer, and in 2006, the agency approved it as a treatment for non-small cell lung cancer. Last year, the FDA also approved Avastin as a metastatic breast cancer treatment, and this past May, it was approved to treat glioblastoma multiforme, an incurable brain cancer.
Avastin has been the subject of other safety concerns. When the FDA approved Avastin for breast cancer patients, it did so against the recommendation of its own advisory panel. The FDA advisory panel recommendation came after agency staffers posted documents on the FDA website noting that while Avastin did extend the period prior to patients’ breast cancer becoming worse, treatment with the drug did not markedly increase survival time. The FDA documents also pointed out that Avastin caused serious side effects, including cardiovascular problems, bowel perforations, and a few deaths. The FDA staff said that those side effects included several patient deaths that were “probably or definitely” due to Avastin.
Avastin has also been linked to a higher risk of blood clots in the veins. And last December, Genentech reported that some Avastin patients had experienced eye inflammation when it was used off-label to treat an eye condition.
According to The Wall Street Journal, the halted Avastin trial was known as E5103. The late-stage trial was testing Avastin in combination with chemotherapy for treatment of early-stage breast cancer. The trial was one of eight studying Avastin as a treatment for preventing relapse after surgery, known as adjuvant therapy. Such studies require careful monitoring, as patients undergoing adjuvant therapy have higher survival rates than those with advanced cancer, the Journal said.
According to a report on Bloomberg.com, the study was slated to enroll 4,950 patients, and so far 3,439 had joined since November 2007. Five of the six cases of congestive heart failure were “resolved” after the patients stopped taking both Avastin and the chemotherapy treatment. There was no information available for the sixth patient, Bloomberg said, but none of the six have died.
According to the Journal, the trial's data safety monitoring board will evaluate the data and determine the next steps. Patients now enrolled in the trial will be able to continue after discussing the developments with their doctor and signing a consent form, the Journal said.