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The drug is usually given as part of a cocktail with chemotherapy drugs in a process that is equal parts science, experience, and experimentation. “We try to pull drugs as fast as we can that are not responding,” says Agus, “but it ends up being mostly trial and error.”

Genetic variations are obviously causing the differences in outcomes, says Winer, although scientists have been unable to locate the culpable DNA, or even identify if its variations occur in the tumors or in the patient.

This is not for want of trying. Genentech says that its researchers have checked out roughly 150 genetic markers in a so-far futile search for genetic biomarkers that might provide clues to differences in outcomes, and that might be used as a diagnostic test to select those who will benefit. The goal is a biomarker test like the one now available for Herceptin, another Genentech breast-cancer treatment that is intended only for women who test positive for more copies of the HER2 gene than normal.

Genentech is currently conducting a large-scale clinical trial involving BRCA1, a gene that in a mutant state is associated with breast cancer, but the results won’t be known for some time.

So far, oncologists continue to give Avastin to many of their patients, and insurers are mostly paying the high price for the drug. Yet Winer doubts that this will continue in this era of escalating health-care costs. “If we can’t find out who benefits, we have a drug that’s very expensive and has some toxicity that has no response; we can’t keep using this forever without targeting the patients it helps,” he says. “We need to find out rather desperately who benefits.”

Winer cites a new initiative by Susan G. Koman for the Cure, a breast-cancer patient advocacy group, to spend $6 million a year for the next five years to research this question.

Possibly the most difficult question for our society to confront is the larger one of how much we are willing to spend for treatments that do not work on most patients.

“We would like to believe that cost should be no object, but that is not reality,” Leonard Saltz, a colon-cancer expert at Memorial Sloan-Kettering Cancer Center, told Forbes recently.

Agus says that if he finds a cancer treatment that will substantially benefit 10 percent of his patients, it’s worth it to give it to everyone with the cancer. But who will pay for this? And what is an acceptable number of beneficiaries? Ten percent? Thirty percent? Three percent? These are not questions that we have had to take seriously in American health care–until now.

So the race continues between rising costs and the search to understand the complexity of reactions to a drug that was rationally conceived, but so far has been as difficult to target as it is to count the stars.

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Tagged: Biomedicine, cancer, drugs, cancer drugs, Avastin

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