The Avastin Paradox

Why does Genentech's anticancer drug work better for some patients than for others?

The quest to design cancer drugs using the latest advances in molecular biology sometimes reminds me of Galileo Galilei and his newfangled telescope. Each time he looked into the nighttime sky with ever more powerful instruments, more stars appeared than before, confounding any notion that a person could ever count them all.

The analogy is this: every time new discoveries and technologies seem to provide answers to medical problems, they also add new layers of complexity and cost.

This has been the case for one of the great breakthroughs in rationalized drug design of the past decade: Avastin, an anticancer pharmaceutical produced by Genentech that uses a wholly different mechanism than the highly toxic chemotherapies that try to kill tumors. Avastin is an antibody that works by choking off the blood supply to a tumor.

Avastin was approved by the Food and Drug Administration to great acclaim in 2004, and is now used for cancers of the colon, breast, lung, and--as of last month--brain. Five years ago, Mark McClellan, then commissioner of the FDA, hailed Avastin's authorization as "proof of the promise offered by biomedical innovation."

Since then, the rational idea behind designing the drug has given way to an unexpectedly complex range of outcomes.

Avastin costs as much as $55,000 for a single course of therapy and earns Roche, which acquired Genentech earlier this year, $4.8 billion annually. Yet the drug ekes out only two more months of increased life span on average than do other cancer drugs.

For some patients, the impact on life span is much greater, though for others the drug does not work at all. Results also vary by cancer type, with breast-cancer patients getting no average life-span increase, and up to 26 percent of patients with brain cancer showing an average increase of four months--with a few patients lasting longer.

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The drug can also allow some--but not all--patients to be treated with fewer side effects, says oncologist David Agus, director of the Westside Cancer Center at the University of Southern California.

"The problem is that we don't know how to identify which patients will respond," says oncologist Eric P. Winer, director of the Breast Oncology Center at the Dana-Farber Cancer Institute. "So we have to try Avastin on lots of people."