Washington Editor

A Phase III setback with Avastin (bevacizumab) in pancreatic cancer is expected to have a minimal impact on Genentech Inc.'s ongoing plans to expand the widely heralded cancer drug's use.

"Even with this announcement, we're still going to be committed to a broad development program," company spokesman Ed Lang told BioWorld Today, noting that the blockbuster product remains in 130 clinical trials across 25 different types of cancer. "With regard to pancreatic cancer, we're still awaiting outcomes from another trial."

Still, he called the South San Francisco company's most recent news "disappointing." The study, which was testing Avastin in combination with gemcitabine chemotherapy as a first-line treatment for the hard-to-treat indication, missed its primary endpoint of overall survival. It was stopped early after an independent interim analysis indicated the unlikelihood of success, but importantly, it was not halted due to safety events, and no new safety concerns were observed.

Genentech did not provide specific numbers, but eventually the data will be presented at an upcoming medical meeting.

The randomized, placebo-controlled trial, which included 602 patients, was labeled CALGB 80303. The statistical plan included pre-specified futility analyses that were conducted and reviewed by an independent data monitoring board, and 200 patients remained in the study when it was stopped. Sponsored by the National Cancer Institute and conducted by a network of researchers led by the Cancer and Leukemia Group B, it was initiated based on results from a single-arm Phase II study that previously tested the combination in that patient population.

Analyst Raymond Christopher of Robert W. Baird & Co. forecasted "little near-term commercial impact" as a result of the study's suspension, he wrote in a research note, adding that pancreatic cancer "represents a smaller market opportunity." Notably, his surveys have shown "minimal existing off-label use" in that space.

Despite the CALGB 80303 misstep, the possibility of expanding Avastin's use into pancreatic cancer is not dead in the water. A randomized Phase III study evaluating the addition of the therapeutic antibody to a standard regimen of gemcitabine and Tarceva (erlotinib) from Genentech, OSI Pharmaceuticals Inc., of Melville, N.Y., and F. Hoffmann-La Roche Ltd., in pancreatic cancer is continuing under Basel, Switzerland-based Roche's management. Called AVITA, it is expected to complete enrollment of 600 patients by the end of this year.

"We want to wait and see what the Avastin and Tarceva trial looks like" before making an ultimate decision on whether to further pursue the pancreatic cancer indication, Lang said. In addition, he noted that another dozen studies of Avastin in pancreatic cancer are under way in the U.S. under the watch of the National Cancer Institute and independent investigators.

The American Cancer Society estimated that 33,730 Americans will be diagnosed this year with pancreatic cancer, which accounts for only about 2 percent of new cancer cases in this country. But it is the fourth leading cause of cancer death in the U.S., because 32,300 will die of it this year. For patients with an advanced form of the disease, the five-year survival rate across all stages is less than 1 percent, and most die within a year of diagnosis.

"It's one of the most difficult cancers to treat," Lang said in characterizing the unmet medical need that the indication represents. "These staggering numbers are just unbelievable."

Avastin, an inhibitor of the vascular endothelial growth factor (VEGF), already is approved in two settings: in combination with intravenous 5-FU-based chemotherapy for the first-line treatment of metastatic colorectal cancer and as a second-line treatment in colorectal cancer.

In addition, the company recently submitted supplemental biologics license applications to expand its use into advanced non-small-cell lung cancer and locally recurrent or metastatic breast cancer. An FDA decision on the lung cancer submission is expected in October, following a priority review. The agency has yet to decide on Genentech's request for priority review on the breast cancer filing.

Those cancers, Raymond said, represent markets in which Avastin's approval and use "is more vital to continued growth." Last quarter, the drug generated $398 million in sales, up 11 percent over the prior three-month period.

On Tuesday, Genentech's stock (NYSE:DNA) lost $1.22 to close at $77.89.