A Phase III study of Avastin (bevacizumab) is resuming after safety worries have been discounted.
The international trial, called AVANT, had been testing the drug's use with two chemotherapy regimens in patients with early stage colon cancer, but was halted earlier this year on reports of a slightly higher death rate not related to colon cancer. After a 60-day review, though, an independent data safety monitoring board has determined that the current safety profile and overall mortality observed in AVANT are consistent with those seen in other early stage colon cancer trials.
That was the source of the worry - a higher rate of adverse events observed in the study arm that includes Avastin and the Xelox chemotherapy regimen, compared to the study's two other arms that include Folfox chemotherapy plus Avastin and Folfox alone. (See BioWorld Today, Feb. 14, 2006.)
The data review from the AVANT trial revealed that mortality from all causes, excluding deaths due to recurrent colon cancer, for Folfox was 0.8 percent (six cases), 0.5 percent (four cases) for Folfox and Avastin, and 1.05 percent (eight cases) for Xelox and Avastin. The rates are consistent with those reported in other adjuvant studies in colon cancer.
The trial moves forward, albeit with a slight tweak to its original protocol: It will include a cardiac monitoring plan comprising an enhanced baseline cardiac assessment and additional basic cardiac investigations to gain better insights on the overall occurrence of cardiac events and sudden deaths. The companies behind the study and the drug, Genentech Inc., of South San Francisco, and F. Hoffmann-La Roche Ltd., of Basel, Switzerland, stressed that there is no indication of an imbalance of cardiac events between AVANT's treatment arms.
Since the trial began in December 2004, about two-thirds of the target number of 3,450 patients has been enrolled. Patients who already had enrolled into the AVANT trial prior to the recruitment suspension continued treatment according to the study protocol.
Another study in the indication, NSABP C-08, has continued without any changes to its protocol evaluating Avastin plus Folfox as an adjuvant treatment for early stage colon cancer. It is being conducted primarily in the U.S. by the National Surgical Adjuvant Breast and Bowel Project (NSABP) in collaboration with the National Cancer Institute.
Avastin is approved as a first-line treatment for metastatic colorectal cancer in combination with 5-FU-based chemotherapy, and the FDA is reviewing applications for expanding its label for relapsed metastatic colorectal cancer and as a first-line treatment for non-squamous, non-small-cell lung cancer. The blockbuster drug, which inhibits the vascular endothelial growth factor (VEGF), also is being studied in breast, kidney, gastrointestinal, prostate, pancreatic and ovarian cancers.
Xelox is made of capecitabine and oxaliplatin, while Folfox includes oxaliplatin, 5-FU and leucovorin together.
Patient recruitment into AVANT, which is being conducted by Roche, will resume upon clearance by the relevant independent review boards and European health authorities.
On Tuesday, shares in Genentech (NYSE:DNA) fell 58 cents to close at $77.86.