Drug curbs relapses, but eligibility tests raise major doubts
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By Judy Peres
Tribune staff reporter
June 5, 2007
Cancer researchers meeting in Chicago had good and bad news Monday for breast-cancer patients who are eligible for treatment with the new-generation drug Herceptin -- at least 40,000 a year in the U.S. alone.
The good news is that Herceptin continues to prevent relapses years after patients stop taking it. The bad news is that the laboratory tests used to determine eligibility appear to be highly inaccurate. That means some women who could benefit from Herceptin don't get it, while others are subjected to the side-effects and high cost of the drug with no hope of a benefit.
"It is a very big deal," said Dr. Larry Norton, head of breast-cancer programs at Memorial Sloan-Kettering Cancer Center in New York.
About one-quarter of breast-cancer patients carry extra copies of a gene called HER2, which makes their tumors more aggressive but also makes them respond to Herceptin, a synthetic antibody that targets the HER2 protein. Herceptin, one of the first in a new generation of targeted cancer drugs, has been shown to reduce the risk of recurrence by about 50 percent. That is a huge benefit, because breast cancer doesn't become life-threatening unless it recurs and spreads to other parts of the body.
On Monday Dr. Edith Perez of the Mayo Clinic location in Jacksonville, Fla., presented trial results showing that, four years after treatment, the women who got Herceptin in addition to chemotherapy were 35 percent more likely to be alive and 52 percent more likely to be relapse-free.
"This is good news for patients," she said.
But one of the slides Perez screened at the annual meeting of the American Society of Clinical Oncology showed that some patients who were classified as HER2-negative got the same benefit as those who tested positive. Perez's data contained too few patients to be statistically significant, but another researcher was scheduled to present similar findings Tuesday in a bigger set of patients.
That caused a buzz among the cancer doctors gathered at McCormick Place, many of whom said the finding raised serious questions about their ability to offer patients the best possible treatment.
Dr. Kathy Albain, director of breast research at Loyola University Health System in Maywood, predicted the data would cause "mass confusion," adding, "It will give me pause to remeasure someone who is initially HER2-negative."
Perez also suggested it might make sense to retest anyone whose first test was negative, just in case it's a false result. "I'm worried about excluding patients who might benefit," she said.
Drug expensive, risky
But Dr. Dennis Slamon of UCLA, who is largely credited with developing Herceptin, noted that false-positive results are also problematic, because the drug costs about $3,000 a month and has sometimes-serious side-effects, including a heightened risk of heart failure.
Dr. Michael Press, a pathologist at the University of Southern California, said as many as one-third of positive antibody tests "could be false-positives."
Slamon called for a high-level task force to figure out how to reduce errors in testing for HER2. As a first step, he said, any negative tumor samples of women who got Herceptin in the clinical trials should be retested by independent, "blinded" pathologists to make sure they're true negatives.
Slamon said there have always been "technical challenges" to determining whether a patient is positive or negative for HER2. One study found that when five pathologists looked at the same slides, they disagreed on the diagnosis in half the cases. "This will bring it to a head," he said, "and that's a good thing."
Early errors found
Shortly after Herceptin was approved by the FDA in 1998, studies began showing that the lab tests to determine if breast-cancer patients should get the drug often yielded false results.
At first it was believed most of the bad results occurred when less-experienced, community laboratories processed the samples or used non-standard test kits. So researchers insisted the tests be performed in a central lab that has processed at least 100 HER2 tests a month for six months.
But Perez said Monday that some of the women who responded to Herceptin in her trial had received negative test results from the central pathology lab that was entrusted with overseeing all the samples.
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